Variant 7-100994057-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.3494G>A(p.Arg1165Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00031 ( 9 hom., cov: 10)

Exomes 𝑓: 0.00045 ( 152 hom. )

Failed GnomAD Quality Control

Consequence

MUC12
NM_001164462.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.40

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=0.0064525604).

BP6

Variant 7-100994057-G-A is Benign according to our data. Variant chr7-100994057-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2657808.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC12	NM_001164462.2 linkuse as main transcript	c.3494G>A	p.Arg1165Gln	missense_variant	2/12	ENST00000536621.6	NP_001157934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC12	ENST00000536621.6 linkuse as main transcript	c.3494G>A	p.Arg1165Gln	missense_variant	2/12	5	NM_001164462.2	ENSP00000441929	A2	Q9UKN1-2
MUC12	ENST00000379442.7 linkuse as main transcript	c.3923G>A	p.Arg1308Gln	missense_variant	5/15	5		ENSP00000368755	P4	Q9UKN1-1

Frequencies

GnomAD3 genomes

AF:

0.000307

AC:

AN:

78290

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00129

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000576

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000683

AC:

AN:

103988

Hom.:

AF XY:

0.000890

AC XY:

AN XY:

55034

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000329

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00287

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000518

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000451

AC:

422

AN:

936616

Hom.:

152

Cov.:

AF XY:

0.000538

AC XY:

249

AN XY:

462574

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00274

Gnomad4 FIN exome

AF:

0.000177

Gnomad4 NFE exome

AF:

0.000334

Gnomad4 OTH exome

AF:

0.000503

GnomAD4 genome

AF:

0.000306

AC:

AN:

78378

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

AN XY:

38026

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00129

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000577

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00151

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

Nov 01, 2022

MUC12: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.1

DANN

Benign

0.61

DEOGEN2

Benign

0.0038

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.0065

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.33

N;N

REVEL

Benign

0.011

Sift

Benign

0.090

T;T

Sift4G

Benign

0.57

T;T

Vest4

0.065

MutPred

0.18

.;Loss of catalytic residue at R1165 (P = 0.0706);

MVP

0.030

ClinPred

0.018

GERP RS

0.71

Varity_R

0.053

gMVP

0.00031

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