Genetic Variant NM_001164462.2:c.3494G>C (chr7-100994057-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001164462.2(MUC12):c.3494G>C(p.Arg1165Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 1,013,280 control chromosomes in the GnomAD database, including 220,775 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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 0.48 ( 15188 hom., cov: 10)

Exomes 𝑓: 0.51 ( 205587 hom. )

Consequence

MUC12
NM_001164462.2 missense

Scores

Clinical Significance

Not reported in ClinVar

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.4416738E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC12	NM_001164462.2 link	c.3494G>C	p.Arg1165Pro	missense_variant	Exon 2 of 12	ENST00000536621.6	NP_001157934.1	Q9UKN1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC12	ENST00000536621.6 link	c.3494G>C	p.Arg1165Pro	missense_variant	Exon 2 of 12	5	NM_001164462.2	ENSP00000441929.1		Q9UKN1-2
MUC12	ENST00000379442.7 link	c.3923G>C	p.Arg1308Pro	missense_variant	Exon 5 of 15	5		ENSP00000368755.3		Q9UKN1-1

Frequencies

GnomAD3 genomes

AF:

0.480

AC:

37315

AN:

77758

Hom.:

15155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.623

Gnomad AMI

AF:

0.523

Gnomad AMR

AF:

0.606

Gnomad ASJ

AF:

0.447

Gnomad EAS

AF:

0.448

Gnomad SAS

AF:

0.342

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.477

Gnomad NFE

AF:

0.405

Gnomad OTH

AF:

0.496

GnomAD3 exomes

AF:

0.562

AC:

58409

AN:

103988

Hom.:

25445

AF XY:

0.549

AC XY:

30209

AN XY:

55034

show subpopulations

Gnomad AFR exome

AF:

0.748

Gnomad AMR exome

AF:

0.724

Gnomad ASJ exome

AF:

0.543

Gnomad EAS exome

AF:

0.560

Gnomad SAS exome

AF:

0.485

Gnomad FIN exome

AF:

0.472

Gnomad NFE exome

AF:

0.497

Gnomad OTH exome

AF:

0.558

GnomAD4 exome

AF:

0.507

AC:

474256

AN:

935432

Hom.:

205587

Cov.:

AF XY:

0.507

AC XY:

234158

AN XY:

462034

show subpopulations

Gnomad4 AFR exome

AF:

0.736

Gnomad4 AMR exome

AF:

0.723

Gnomad4 ASJ exome

AF:

0.535

Gnomad4 EAS exome

AF:

0.605

Gnomad4 SAS exome

AF:

0.485

Gnomad4 FIN exome

AF:

0.472

Gnomad4 NFE exome

AF:

0.487

Gnomad4 OTH exome

AF:

0.539

GnomAD4 genome

AF:

0.480

AC:

37390

AN:

77848

Hom.:

15188

Cov.:

AF XY:

0.480

AC XY:

18133

AN XY:

37764

show subpopulations

Gnomad4 AFR

AF:

0.624

Gnomad4 AMR

AF:

0.606

Gnomad4 ASJ

AF:

0.447

Gnomad4 EAS

AF:

0.450

Gnomad4 SAS

AF:

0.344

Gnomad4 FIN

AF:

0.308

Gnomad4 NFE

AF:

0.405

Gnomad4 OTH

AF:

0.497

ExAC

AF:

0.494

AC:

8196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.5

DANN

Benign

0.30

DEOGEN2

Benign

0.0039

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.000020

LIST_S2

Benign

0.32

T;T

MetaRNN

Benign

0.0000024

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-2.1

N;.

PrimateAI

Benign

0.48

PROVEAN

Benign

0.67

N;N

REVEL

Benign

0.013

Sift

Benign

1.0

T;T

Sift4G

Benign

0.26

T;T

Vest4

0.059

ClinPred

0.0045

GERP RS

0.71

Varity_R

0.11

gMVP

0.0014

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