Variant chr7-101032455-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000306151.9(MUC17):c.1039G>A(p.Ala347Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,613,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

MUC17
ENST00000306151.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.61

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:

MUC17 (HGNC:):

MUC17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.047061414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC17	NM_001040105.2 linkuse as main transcript	c.1039G>A	p.Ala347Thr	missense_variant	3/13	ENST00000306151.9	NP_001035194.1	Q685J3-1
MUC17	NR_133665.2 linkuse as main transcript	n.1094G>A		non_coding_transcript_exon_variant	3/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC17	ENST00000306151.9 linkuse as main transcript	c.1039G>A	p.Ala347Thr	missense_variant	3/13	1	NM_001040105.2	ENSP00000302716.4		Q685J3-1
MUC17	ENST00000379439.3 linkuse as main transcript	n.1039G>A		non_coding_transcript_exon_variant	3/12	1		ENSP00000368751.3		E7EPM4

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000677

AC:

AN:

251104

Hom.:

AF XY:

0.0000590

AC XY:

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000540

AC:

AN:

1461628

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000504

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000138

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000503

Hom.:

Bravo

AF:

0.000132

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.1039G>A (p.A347T) alteration is located in exon 3 (coding exon 3) of the MUC17 gene. This alteration results from a G to A substitution at nucleotide position 1039, causing the alanine (A) at amino acid position 347 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.51

DANN

Benign

0.43

DEOGEN2

Benign

0.017

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00054

LIST_S2

Benign

0.36

M_CAP

Benign

0.00084

MetaRNN

Benign

0.047

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

0.21

REVEL

Benign

0.0060

Sift

Benign

0.25

Polyphen

0.023

Vest4

0.027

MutPred

0.14

Gain of glycosylation at A347 (P = 0.0036);

MVP

0.014

ClinPred

0.034

GERP RS

0.23

Varity_R

0.025

gMVP

0.0055

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over