Genetic Variant MUC17:p.Thr339Met (chr7-101032432-C-T) – 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.1016C>T(p.Thr339Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 1,609,854 control chromosomes in the GnomAD database, including 1,758 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 0.016 ( 148 hom., cov: 33)

Exomes 𝑓: 0.016 ( 1610 hom. )

Consequence

MUC17
NM_001040105.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.72

Publications

12 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=0.0010945797).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 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.1016C>T	p.Thr339Met	missense	Exon 3 of 13	NP_001035194.1	Q685J3-1
	MUC17	NR_133665.2		n.1071C>T		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.1016C>T	p.Thr339Met	missense	Exon 3 of 13	ENSP00000302716.4	Q685J3-1
MUC17	ENST00000379439.3	TSL:1	n.1016C>T		non_coding_transcript_exon	Exon 3 of 12	ENSP00000368751.3	E7EPM4
MUC12-AS1	ENST00000844128.1		n.345-17993G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2374

AN:

149008

Hom.:

147

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.178

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.0295

Gnomad MID

AF:

0.00360

Gnomad NFE

AF:

0.00136

Gnomad OTH

AF:

0.0181

GnomAD2 exomes

AF:

0.0402

AC:

10064

AN:

250418

AF XY:

0.0428

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.0504

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.167

Gnomad FIN exome

AF:

0.0303

Gnomad NFE exome

AF:

0.00149

Gnomad OTH exome

AF:

0.0239

GnomAD4 exome

AF:

0.0165

AC:

24045

AN:

1460720

Hom.:

1610

Cov.:

AF XY:

0.0198

AC XY:

14352

AN XY:

726612

show subpopulations

African (AFR)

AF:

0.00120

AC:

AN:

33456

American (AMR)

AF:

0.0449

AC:

2003

AN:

44590

Ashkenazi Jewish (ASJ)

AF:

0.0000384

AC:

AN:

26048

East Asian (EAS)

AF:

0.164

AC:

6497

AN:

39682

South Asian (SAS)

AF:

0.135

AC:

11646

AN:

86116

European-Finnish (FIN)

AF:

0.0279

AC:

1490

AN:

53350

Middle Eastern (MID)

AF:

0.00902

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000744

AC:

827

AN:

1111380

Other (OTH)

AF:

0.0247

AC:

1489

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

1680

3360

5040

6720

8400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

302

604

906

1208

1510

<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:

0.0160

AC:

2379

AN:

149134

Hom.:

148

Cov.:

AF XY:

0.0201

AC XY:

1467

AN XY:

72982

show subpopulations

African (AFR)

AF:

0.00223

AC:

AN:

40356

American (AMR)

AF:

0.0140

AC:

211

AN:

15044

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3438

East Asian (EAS)

AF:

0.178

AC:

889

AN:

5008

South Asian (SAS)

AF:

0.159

AC:

746

AN:

4688

European-Finnish (FIN)

AF:

0.0295

AC:

306

AN:

10376

Middle Eastern (MID)

AF:

0.00382

AC:

AN:

262

European-Non Finnish (NFE)

AF:

0.00136

AC:

AN:

67002

Other (OTH)

AF:

0.0218

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

108

216

323

431

539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.00794

Hom.:

124

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.0393

AC:

4767

Asia WGS

AF:

0.193

AC:

668

AN:

3478

EpiCase

AF:

0.000984

EpiControl

AF:

0.00101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.034

(source)

DANN

Benign

0.14

DEOGEN2

Benign

0.017

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.00062

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0011

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-2.1

PhyloP100

-1.7

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.66

REVEL

Benign

0.033

Sift

Benign

0.20

Polyphen

0.014

Vest4

0.040

ClinPred

0.0055

GERP RS

-2.4

Varity_R

0.013

gMVP

0.027

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