Variant 7-100993961-G-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_001164462.2(MUC12):c.3398G>A(p.Arg1133His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00085 ( 20 hom., cov: 13)

Exomes 𝑓: 0.022 ( 30 hom. )

Failed GnomAD Quality Control

Consequence

MUC12
NM_001164462.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.69

Variant links:

Genes affected

MUC12 (HGNC:7510): (mucin 12, cell surface associated) This gene encodes an integral membrane glycoprotein that is a member of the mucin family. Mucins are O-glycosylated proteins that play an essential role in forming protective mucous barriers on epithelial surfaces and have been implicated in epithelial renewal and differentiation. These glycoproteins also play a role in intracellular signaling. This protein is expressed on the apical membrane surface of epithelial cells that line the mucosal surfaces of many different tissues including the colon, pancreas, prostate, and uterus. The expression of this gene is downregulated in colorectal cancer tissue. [provided by RefSeq, Apr 2017]

MUC12 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=0.00433439).

BP6

Variant 7-100993961-G-A is Benign according to our data. Variant chr7-100993961-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2657807.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC12	NM_001164462.2 link	c.3398G>A	p.Arg1133His	missense_variant	2/12	ENST00000536621.6	NP_001157934.1	Q9UKN1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC12	ENST00000536621.6 link	c.3398G>A	p.Arg1133His	missense_variant	2/12	5	NM_001164462.2	ENSP00000441929.1		Q9UKN1-2
MUC12	ENST00000379442.7 link	c.3827G>A	p.Arg1276His	missense_variant	5/15	5		ENSP00000368755.3		Q9UKN1-1

Frequencies

GnomAD3 genomes

AF:

0.000847

AC:

AN:

92058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00240

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000341

Gnomad OTH

AF:

0.00222

GnomAD3 exomes

AF:

0.000403

AC:

AN:

104196

Hom.:

AF XY:

0.000362

AC XY:

AN XY:

55186

show subpopulations

Gnomad AFR exome

AF:

0.00352

Gnomad AMR exome

AF:

0.000240

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000449

Gnomad SAS exome

AF:

0.000119

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000247

Gnomad OTH exome

AF:

0.000645

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0225

AC:

24758

AN:

1102748

Hom.:

Cov.:

AF XY:

0.0225

AC XY:

12257

AN XY:

544788

show subpopulations

Gnomad4 AFR exome

AF:

0.0200

Gnomad4 AMR exome

AF:

0.00714

Gnomad4 ASJ exome

AF:

0.0122

Gnomad4 EAS exome

AF:

0.0210

Gnomad4 SAS exome

AF:

0.0243

Gnomad4 FIN exome

AF:

0.0146

Gnomad4 NFE exome

AF:

0.0237

Gnomad4 OTH exome

AF:

0.0190

GnomAD4 genome

AF:

0.000846

AC:

AN:

92166

Hom.:

Cov.:

AF XY:

0.000922

AC XY:

AN XY:

44468

show subpopulations

Gnomad4 AFR

AF:

0.00240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000341

Gnomad4 OTH

AF:

0.00219

Alfa

AF:

0.000457

Hom.:

ExAC

AF:

0.000852

AC:

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

Aug 01, 2023

MUC12: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.2

DANN

Benign

0.41

DEOGEN2

Benign

0.0046

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00033

LIST_S2

Benign

0.34

T;T

MetaRNN

Benign

0.0043

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.0

N;.

PrimateAI

Benign

0.45

PROVEAN

Benign

0.19

N;N

REVEL

Benign

0.0020

Sift

Benign

1.0

T;T

Sift4G

Benign

0.18

T;T

Vest4

0.013

MVP

0.014

ClinPred

0.0048

GERP RS

-1.4

Varity_R

0.028

gMVP

0.0013

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