Variant 7-101032257-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001040105.2(MUC17):c.841C>A(p.Pro281Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00516 in 1,613,782 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0053 ( 31 hom. )

Consequence

MUC17
NM_001040105.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.45

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056450367).

BP6

Variant 7-101032257-C-A is Benign according to our data. Variant chr7-101032257-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2657834.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC17	NM_001040105.2 linkuse as main transcript	c.841C>A	p.Pro281Thr	missense_variant	3/13	ENST00000306151.9	NP_001035194.1
MUC17	NR_133665.2 linkuse as main transcript	n.896C>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.841C>A	p.Pro281Thr	missense_variant	3/13	1	NM_001040105.2	ENSP00000302716	P1	Q685J3-1
MUC17	ENST00000379439.3 linkuse as main transcript	c.841C>A	p.Pro281Thr	missense_variant, NMD_transcript_variant	3/12	1		ENSP00000368751

Frequencies

GnomAD3 genomes

AF:

0.00369

AC:

562

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00688

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00372

AC:

935

AN:

251060

Hom.:

AF XY:

0.00379

AC XY:

514

AN XY:

135684

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.000897

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000557

Gnomad FIN exome

AF:

0.00255

Gnomad NFE exome

AF:

0.00682

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00531

AC:

7758

AN:

1461514

Hom.:

Cov.:

AF XY:

0.00510

AC XY:

3708

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.00141

Gnomad4 ASJ exome

AF:

0.000996

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000812

Gnomad4 FIN exome

AF:

0.00279

Gnomad4 NFE exome

AF:

0.00648

Gnomad4 OTH exome

AF:

0.00344

GnomAD4 genome

AF:

0.00369

AC:

562

AN:

152268

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

249

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000554

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.00688

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00561

Hom.:

Bravo

AF:

0.00323

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00721

AC:

ExAC

AF:

0.00399

AC:

484

EpiCase

AF:

0.00611

EpiControl

AF:

0.00622

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

MUC17: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.38

DANN

Benign

0.31

DEOGEN2

Benign

0.018

Eigen

Benign

-0.90

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.21

M_CAP

Benign

0.00084

MetaRNN

Benign

0.0056

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.28

REVEL

Benign

0.055

Sift

Pathogenic

0.0

Polyphen

0.95

Vest4

0.091

MVP

0.040

ClinPred

0.018

GERP RS

0.36

Varity_R

0.070

gMVP

0.0066

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