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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC17	NM_001040105.2 link	c.1016C>T	p.Thr339Met	missense_variant	Exon 3 of 13	ENST00000306151.9	NP_001035194.1
MUC17	NR_133665.2 link	n.1071C>T		non_coding_transcript_exon_variant	Exon 3 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
MUC17	ENST00000306151.9 link	c.1016C>T	p.Thr339Met	missense_variant	Exon 3 of 13	1	NM_001040105.2	ENSP00000302716.4
MUC17	ENST00000379439.3 link	n.1016C>T		non_coding_transcript_exon_variant	Exon 3 of 12	1		ENSP00000368751.3
MUC12-AS1	ENST00000844128.1 link	n.345-17993G>A		intron_variant	Intron 1 of 1
MUC12-AS1	ENST00000844129.1 link	n.340-17165G>A		intron_variant	Intron 1 of 2

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over