Genetic Variant MUC12:p.Arg1133Pro (chr7-100993961-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001164462.2(MUC12):c.3398G>C(p.Arg1133Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000225 in 1,290,508 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 0.00023 ( 6 hom., cov: 13)

Exomes 𝑓: 0.0000067 ( 2 hom. )

Consequence

MUC12
NM_001164462.2 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.058499128).

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC12	NM_001164462.2 link	c.3398G>C	p.Arg1133Pro	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.3398G>C	p.Arg1133Pro	missense_variant	Exon 2 of 12	5	NM_001164462.2	ENSP00000441929.1		Q9UKN1-2
MUC12	ENST00000379442.7 link	c.3827G>C	p.Arg1276Pro	missense_variant	Exon 5 of 15	5		ENSP00000368755.3		Q9UKN1-1

Frequencies

GnomAD3 genomes

AF:

0.000228

AC:

AN:

92134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000591

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000577

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000192

AC:

AN:

104196

Hom.:

AF XY:

0.0000181

AC XY:

AN XY:

55186

show subpopulations

Gnomad AFR exome

AF:

0.000176

Gnomad AMR exome

AF:

0.0000479

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000668

AC:

AN:

1198374

Hom.:

Cov.:

AF XY:

0.00000169

AC XY:

AN XY:

592096

show subpopulations

Gnomad4 AFR exome

AF:

0.000254

Gnomad4 AMR exome

AF:

0.0000302

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000228

AC:

AN:

92134

Hom.:

Cov.:

AF XY:

0.000248

AC XY:

AN XY:

44422

show subpopulations

Gnomad4 AFR

AF:

0.000591

Gnomad4 AMR

AF:

0.000577

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.74

CADD

Benign

2.4

DANN

Benign

0.35

DEOGEN2

Benign

0.0039

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.25

T;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.058

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.34

N;.

PrimateAI

Benign

0.45

PROVEAN

Benign

0.020

N;N

REVEL

Benign

0.0060

Sift

Benign

0.039

D;D

Sift4G

Benign

0.22

T;T

Vest4

0.11

MutPred

0.20

.;Gain of glycosylation at R1133 (P = 0.0143);

MVP

0.081

ClinPred

0.013

GERP RS

-1.4

Varity_R

0.11

gMVP

0.0017

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