1-45331833-C-G

Variant names:

Variant summary

Our verdict is The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025): 1P and 5B. O4_SupportingB1_StrongB3_Supporting

The NM_001048174.2(MUTYH):c.930G>C (p.Gln310His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The gene MUTYH is a cancer driver gene (CancerMine: 2 driver citations). The variant allele was found at a cumulative frequency of 0.261 (AC=418,548) in the gnomAD database across 1,603,502 control chromosomes, including 56,797 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.472. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★). Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.Q310E: Uncertain_significance (ClinVar VariationId 4112922, 1 star); p.Q310H: Conflicting_classifications_of_pathogenicity (ClinVar VariationId 492713); p.Q310K: Uncertain_significance (ClinVar VariationId 4112921, 1 star); p.Q310L: Benign (ClinVar VariationId 485901, 1 star); p.Q310P: Uncertain_significance (ClinVar VariationId 4112923, 1 star); p.Q310= (synonymous): Likely_benign (ClinVar VariationId 1740087, 1 star); p.Q310R: Conflicting_classifications_of_pathogenicity (ClinVar VariationId 127836); p.Q310R: Benign/Likely_benign (ClinVar VariationId 142590, 2 stars) The variant has been observed in cBioPortal in 11 samples across 6 studies and 10 cancer types; somatic enrichment level: SUPPORTING (Observed repeatedly in cBioPortal somatic datasets.). This exact variant is curated in the UniProt human variants database as Uncertain Significance; it is also listed as a COSMIC curated somatic variant.

Frequency

Genomes: 𝑓 0.27 ( 5852 hom., cov: 33)

Exomes 𝑓: 0.26 ( 50945 hom. )

Consequence

MUTYH
NM_001048174.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:22O:1

Conservation

PhyloP100: -0.265

Publications

182 publications found

Variant links:

Genes affected

MUTYH (HGNC:7527): (mutY DNA glycosylase) This gene encodes a DNA glycosylase involved in oxidative DNA damage repair. The enzyme excises adenine bases from the DNA backbone at sites where adenine is inappropriately paired with guanine, cytosine, or 8-oxo-7,8-dihydroguanine, a major oxidatively damaged DNA lesion. The protein is localized to the nucleus and mitochondria. This gene product is thought to play a role in signaling apoptosis by the introduction of single-strand breaks following oxidative damage. Mutations in this gene result in heritable predisposition to colorectal cancer, termed MUTYH-associated polyposis (MAP). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]

MUTYH Gene-Disease associations (from GenCC):

familial adenomatous polyposis 2
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, G2P, ClinGen
colorectal cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
familial ovarian cancer
Inheritance: AD, AR Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD, AR Classification: NO_KNOWN Submitted by: ClinGen

MUTYH links:

ENSG00000288208 (HGNC:):

ENSG00000288208 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001048174.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 points.

GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.472 — exceeds 1% threshold (B1 applied)

Computational evidence does not support a deleterious effect; Missense variant — primary computational scorer does not support an oncogenic/deleterious effect; supports B3

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001048174.2. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MUTYH	NM_001128425.2	MANE Plus Clinical	c.1014G>C	p.Gln338His	missense	Exon 12 of 16	NP_001121897.1	E5KP25
MUTYH	NM_001048174.2	MANE Select	c.930G>C	p.Gln310His	missense	Exon 12 of 16	NP_001041639.1	Q9UIF7-6
MUTYH	NM_012222.3		c.1005G>C	p.Gln335His	missense	Exon 12 of 16	NP_036354.1	Q9UIF7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MUTYH	ENST00000710952.2	MANE Plus Clinical	c.1014G>C	p.Gln338His	missense	Exon 12 of 16	ENSP00000518552.2	E5KP25
MUTYH	ENST00000456914.7	TSL:1 MANE Select	c.930G>C	p.Gln310His	missense	Exon 12 of 16	ENSP00000407590.2	Q9UIF7-6
MUTYH	ENST00000372098.7	TSL:1	c.1005G>C	p.Gln335His	missense	Exon 12 of 16	ENSP00000361170.3	Q9UIF7-1

Frequencies

GnomAD3 genomes

AF:

0.269

AC:

40958

AN:

152016

Hom.:

5824

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.274

Gnomad AMR

AF:

0.400

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.412

Gnomad SAS

AF:

0.238

Gnomad FIN

AF:

0.215

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.243

Gnomad OTH

AF:

0.297

GnomAD2 exomes

AF:

0.290

AC:

67377

AN:

232316

AF XY:

0.277

show subpopulations

Gnomad AFR exome

AF:

0.263

Gnomad AMR exome

AF:

0.488

Gnomad ASJ exome

AF:

0.263

Gnomad EAS exome

AF:

0.397

Gnomad FIN exome

AF:

0.220

Gnomad NFE exome

AF:

0.244

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.260

AC:

377531

AN:

1451368

Hom.:

50945

Cov.:

AF XY:

0.257

AC XY:

185520

AN XY:

721162

show subpopulations

African (AFR)

AF:

0.266

AC:

8835

AN:

33194

American (AMR)

AF:

0.477

AC:

20523

AN:

43026

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

6710

AN:

25756

East Asian (EAS)

AF:

0.420

AC:

16507

AN:

39306

South Asian (SAS)

AF:

0.233

AC:

19899

AN:

85350

European-Finnish (FIN)

AF:

0.228

AC:

11904

AN:

52316

Middle Eastern (MID)

AF:

0.292

AC:

1643

AN:

5630

European-Non Finnish (NFE)

AF:

0.249

AC:

275322

AN:

1106868

Other (OTH)

AF:

0.270

AC:

16188

AN:

59922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

18127

36253

54380

72506

90633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9744

19488

29232

38976

48720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.270

AC:

41017

AN:

152134

Hom.:

5852

Cov.:

AF XY:

0.270

AC XY:

20054

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.263

AC:

10933

AN:

41514

American (AMR)

AF:

0.401

AC:

6123

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.262

AC:

909

AN:

3470

East Asian (EAS)

AF:

0.412

AC:

2127

AN:

5162

South Asian (SAS)

AF:

0.238

AC:

1147

AN:

4824

European-Finnish (FIN)

AF:

0.215

AC:

2275

AN:

10594

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.243

AC:

16532

AN:

67978

Other (OTH)

AF:

0.305

AC:

642

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1552

3103

4655

6206

7758

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.250

Hom.:

1622

Bravo

AF:

0.287

Asia WGS

AF:

0.359

AC:

1247

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.457

AC:

56071

AN:

122724

Turkish Variome

AF:

0.261

AC:

1701

AN:

6524

Hom.:

239

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.376

AC:

3373

AN:

8960

Hom.:

613

ABraOM SABE-WGS-1171

AF:

0.308

AC:

721

AN:

2342

Hom.:

120

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (9)

Familial adenomatous polyposis 2 (4)

Hereditary cancer-predisposing syndrome (4)

not provided (4)

Carcinoma of colon (1)

Familial multiple polyposis syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.086

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0010

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.7

PhyloP100

-0.27

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.0

REVEL

Benign

0.043

Sift

Benign

0.17

Sift4G

Benign

0.12

PromoterAI

-0.00020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.51

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over