Genetic Variant NM_001040105.2:c.11794G>C (chr7-101043210-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001040105.2(MUC17):c.11794G>C(p.Gly3932Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00634 in 1,614,098 control chromosomes in the GnomAD database, including 618 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0078 ( 38 hom., cov: 33)

Exomes 𝑓: 0.0062 ( 580 hom. )

Consequence

MUC17
NM_001040105.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0670

Publications

13 publications found

Variant links:

Genes affected

MUC17 (HGNC:16800): (mucin 17, cell surface associated) The protein encoded by this gene is a membrane-bound mucin that provides protection to gut epithelial cells. The encoded protein contains about 60 tandem repeats, with each repeat being around 60 aa. N-glycosylation enables the encoded protein to localize on the cell surface, while the C-terminus interacts with the scaffold protein PDZ domain containing 1 (PDZK1). Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Nov 2015]

MUC17 links:

MUC12-AS1 (HGNC:40382): (MUC12 antisense RNA 1)

MUC12-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002008915).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040105.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC17	NM_001040105.2	MANE Select	c.11794G>C	p.Gly3932Arg	missense	Exon 3 of 13	NP_001035194.1	Q685J3-1
	MUC17	NR_133665.2		n.11849G>C		non_coding_transcript_exon	Exon 3 of 12

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MUC17	ENST00000306151.9	TSL:1 MANE Select	c.11794G>C	p.Gly3932Arg	missense	Exon 3 of 13	ENSP00000302716.4	Q685J3-1
MUC17	ENST00000379439.3	TSL:1	n.11794G>C		non_coding_transcript_exon	Exon 3 of 12	ENSP00000368751.3	E7EPM4
MUC12-AS1	ENST00000844128.1		n.344+20775C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00776

AC:

1181

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0177

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.00641

Gnomad FIN

AF:

0.0184

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.00527

GnomAD2 exomes

AF:

0.0142

AC:

3555

AN:

251190

AF XY:

0.0129

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.0232

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.117

Gnomad FIN exome

AF:

0.0164

Gnomad NFE exome

AF:

0.000784

Gnomad OTH exome

AF:

0.00929

GnomAD4 exome

AF:

0.00619

AC:

9052

AN:

1461886

Hom.:

580

Cov.:

AF XY:

0.00600

AC XY:

4362

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.000299

AC:

AN:

33480

American (AMR)

AF:

0.0219

AC:

981

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000612

AC:

AN:

26136

East Asian (EAS)

AF:

0.158

AC:

6258

AN:

39700

South Asian (SAS)

AF:

0.00278

AC:

240

AN:

86258

European-Finnish (FIN)

AF:

0.0148

AC:

790

AN:

53412

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000360

AC:

400

AN:

1112012

Other (OTH)

AF:

0.00581

AC:

351

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

634

1268

1901

2535

3169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

216

324

432

540

<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:

0.00777

AC:

1182

AN:

152212

Hom.:

Cov.:

AF XY:

0.00962

AC XY:

716

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.000794

AC:

AN:

41536

American (AMR)

AF:

0.0178

AC:

272

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3466

East Asian (EAS)

AF:

0.115

AC:

594

AN:

5168

South Asian (SAS)

AF:

0.00600

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0184

AC:

195

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000676

AC:

AN:

68006

Other (OTH)

AF:

0.00569

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

105

158

210

263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00483

Hom.:

Bravo

AF:

0.00829

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.0133

AC:

1610

Asia WGS

AF:

0.0430

AC:

149

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.1

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.018

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.40

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.3

PhyloP100

-0.067

PrimateAI

Benign

0.17

PROVEAN

Benign

-0.070

REVEL

Benign

0.030

Sift

Benign

0.23

Polyphen

1.0

Vest4

0.026

MutPred

0.28

Loss of loop (P = 0.0203)

ClinPred

0.0094

GERP RS

-0.77

Varity_R

0.040

gMVP

0.021

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over