Genetic Variant NM_001164462.2:c.3398G>T (chr7-100993961-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001164462.2(MUC12):c.3398G>T(p.Arg1133Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1133H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 13)

Failed GnomAD Quality Control

Consequence

MUC12
NM_001164462.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.69

Publications

7 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06560138).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164462.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC12	NM_001164462.2	MANE Select	c.3398G>T	p.Arg1133Leu	missense	Exon 2 of 12	NP_001157934.1	Q9UKN1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MUC12	ENST00000536621.6	TSL:5 MANE Select	c.3398G>T	p.Arg1133Leu	missense	Exon 2 of 12	ENSP00000441929.1	Q9UKN1-2
MUC12	ENST00000379442.7	TSL:5	c.3827G>T	p.Arg1276Leu	missense	Exon 5 of 15	ENSP00000368755.3	Q9UKN1-1
MUC12	ENST00000895813.1		c.68-12510G>T		intron	N/A	ENSP00000565872.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

92134

Hom.:

Cov.:

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

92134

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

44422

African (AFR)

AF:

0.00

AC:

AN:

25396

American (AMR)

AF:

0.00

AC:

AN:

10398

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2292

East Asian (EAS)

AF:

0.00

AC:

AN:

2634

South Asian (SAS)

AF:

0.00

AC:

AN:

2696

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

226

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

41062

Other (OTH)

AF:

0.00

AC:

AN:

1354

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.000114

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.2

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.0043

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.29

M_CAP

Benign

0.0068

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

PhyloP100

-1.7

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.62

REVEL

Benign

0.0060

Sift

Benign

0.050

Sift4G

Benign

0.27

Vest4

0.050

MutPred

0.21

Loss of phosphorylation at T1131 (P = 0.0681)

MVP

0.055

ClinPred

0.031

GERP RS

-1.4

Varity_R

0.054

gMVP

0.0016

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over