Variant 7-101004836-C-G 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.14273C>G(p.Thr4758Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 1,537,424 control chromosomes in the GnomAD database, including 201,039 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.47 ( 16967 hom., cov: 31)

Exomes 𝑓: 0.51 ( 184072 hom. )

Consequence

MUC12
NM_001164462.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.604

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4604191E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC12	NM_001164462.2 link	c.14273C>G	p.Thr4758Arg	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.14273C>G	p.Thr4758Arg	missense_variant	2/12	5	NM_001164462.2	ENSP00000441929.1		Q9UKN1-2
MUC12	ENST00000379442.7 link	c.14702C>G	p.Thr4901Arg	missense_variant	5/15	5		ENSP00000368755.3		Q9UKN1-1

Frequencies

GnomAD3 genomes

AF:

0.468

AC:

71085

AN:

151752

Hom.:

16968

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.481

Gnomad AMR

AF:

0.390

Gnomad ASJ

AF:

0.502

Gnomad EAS

AF:

0.603

Gnomad SAS

AF:

0.498

Gnomad FIN

AF:

0.503

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.519

Gnomad OTH

AF:

0.455

GnomAD3 exomes

AF:

0.483

AC:

70743

AN:

146590

Hom.:

17435

AF XY:

0.487

AC XY:

37906

AN XY:

77788

show subpopulations

Gnomad AFR exome

AF:

0.386

Gnomad AMR exome

AF:

0.371

Gnomad ASJ exome

AF:

0.503

Gnomad EAS exome

AF:

0.602

Gnomad SAS exome

AF:

0.487

Gnomad FIN exome

AF:

0.509

Gnomad NFE exome

AF:

0.512

Gnomad OTH exome

AF:

0.493

GnomAD4 exome

AF:

0.513

AC:

711396

AN:

1385554

Hom.:

184072

Cov.:

AF XY:

0.513

AC XY:

351029

AN XY:

683670

show subpopulations

Gnomad4 AFR exome

AF:

0.390

Gnomad4 AMR exome

AF:

0.368

Gnomad4 ASJ exome

AF:

0.501

Gnomad4 EAS exome

AF:

0.597

Gnomad4 SAS exome

AF:

0.492

Gnomad4 FIN exome

AF:

0.504

Gnomad4 NFE exome

AF:

0.522

Gnomad4 OTH exome

AF:

0.508

GnomAD4 genome

AF:

0.468

AC:

71111

AN:

151870

Hom.:

16967

Cov.:

AF XY:

0.465

AC XY:

34495

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.383

Gnomad4 AMR

AF:

0.390

Gnomad4 ASJ

AF:

0.502

Gnomad4 EAS

AF:

0.603

Gnomad4 SAS

AF:

0.498

Gnomad4 FIN

AF:

0.503

Gnomad4 NFE

AF:

0.519

Gnomad4 OTH

AF:

0.453

Alfa

AF:

0.482

Hom.:

3283

Bravo

AF:

0.458

TwinsUK

AF:

0.523

AC:

1938

ALSPAC

AF:

0.519

AC:

2001

ESP6500AA

AF:

0.405

AC:

560

ESP6500EA

AF:

0.514

AC:

1634

ExAC

AF:

0.465

AC:

11226

Asia WGS

AF:

0.509

AC:

1770

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.9

DANN

Benign

0.13

DEOGEN2

Benign

0.048

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.21

T;T

MetaRNN

Benign

0.000015

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.7

L;.

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.011

Sift

Benign

0.48

T;T

Sift4G

Uncertain

0.032

D;D

Vest4

0.021

ClinPred

0.0072

GERP RS

-0.98

Varity_R

0.12

gMVP

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over