Variant 7-100999174-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001164462.2(MUC12):c.8611G>A(p.Ala2871Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0267 in 79,908 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 not provided (no stars).

Frequency

Genomes: 𝑓 0.027 ( 0 hom., cov: 30)

Exomes 𝑓: 0.020 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MUC12
NM_001164462.2 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -1.53

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025514364).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC12	NM_001164462.2 linkuse as main transcript	c.8611G>A	p.Ala2871Thr	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.8611G>A	p.Ala2871Thr	missense_variant	2/12	5	NM_001164462.2	ENSP00000441929	A2	Q9UKN1-2
MUC12	ENST00000379442.7 linkuse as main transcript	c.9040G>A	p.Ala3014Thr	missense_variant	5/15	5		ENSP00000368755	P4	Q9UKN1-1

Frequencies

GnomAD3 genomes

AF:

0.0267

AC:

2128

AN:

79840

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0360

Gnomad AMI

AF:

0.00338

Gnomad AMR

AF:

0.0173

Gnomad ASJ

AF:

0.00626

Gnomad EAS

AF:

0.0577

Gnomad SAS

AF:

0.0495

Gnomad FIN

AF:

0.0222

Gnomad MID

AF:

0.0146

Gnomad NFE

AF:

0.0202

Gnomad OTH

AF:

0.0299

GnomAD3 exomes

AF:

0.0235

AC:

1608

AN:

68304

Hom.:

AF XY:

0.0227

AC XY:

795

AN XY:

35084

show subpopulations

Gnomad AFR exome

AF:

0.0359

Gnomad AMR exome

AF:

0.0212

Gnomad ASJ exome

AF:

0.00629

Gnomad EAS exome

AF:

0.0376

Gnomad SAS exome

AF:

0.0280

Gnomad FIN exome

AF:

0.0114

Gnomad NFE exome

AF:

0.0207

Gnomad OTH exome

AF:

0.0211

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0200

AC:

10366

AN:

519142

Hom.:

Cov.:

AF XY:

0.0191

AC XY:

5009

AN XY:

262508

show subpopulations

Gnomad4 AFR exome

AF:

0.0300

Gnomad4 AMR exome

AF:

0.0132

Gnomad4 ASJ exome

AF:

0.00131

Gnomad4 EAS exome

AF:

0.0415

Gnomad4 SAS exome

AF:

0.0147

Gnomad4 FIN exome

AF:

0.00266

Gnomad4 NFE exome

AF:

0.0209

Gnomad4 OTH exome

AF:

0.0165

GnomAD4 genome

AF:

0.0267

AC:

2135

AN:

79908

Hom.:

Cov.:

AF XY:

0.0278

AC XY:

1049

AN XY:

37692

show subpopulations

Gnomad4 AFR

AF:

0.0359

Gnomad4 AMR

AF:

0.0175

Gnomad4 ASJ

AF:

0.00626

Gnomad4 EAS

AF:

0.0581

Gnomad4 SAS

AF:

0.0498

Gnomad4 FIN

AF:

0.0222

Gnomad4 NFE

AF:

0.0202

Gnomad4 OTH

AF:

0.0323

Alfa

AF:

0.0584

Hom.:

ExAC

AF:

0.157

AC:

2384

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

not provided, no classification provided

literature only

James Howe Lab, University of Iowa Hospital and Clinics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.8

DANN

Benign

0.93

DEOGEN2

Benign

0.0032

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0056

LIST_S2

Benign

0.37

T;T

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.97

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.83

N;N

REVEL

Benign

0.032

Sift

Benign

0.053

T;D

Sift4G

Benign

0.29

T;T

Vest4

0.011

ClinPred

0.0062

GERP RS

0.47

Varity_R

0.089

gMVP

0.013

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