Genetic Variant NM_001164462.2:c.3369G>A (chr7-100993932-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_001164462.2(MUC12):c.3369G>A(p.Leu1123Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.019 ( 3 hom., cov: 13)

Exomes 𝑓: 0.47 ( 174809 hom. )

Failed GnomAD Quality Control

Consequence

MUC12
NM_001164462.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.357

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.04).

BP7

Synonymous conserved (PhyloP=-0.357 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC12	NM_001164462.2 link	c.3369G>A	p.Leu1123Leu	synonymous_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.3369G>A	p.Leu1123Leu	synonymous_variant	Exon 2 of 12	5	NM_001164462.2	ENSP00000441929.1		Q9UKN1-2
MUC12	ENST00000379442.7 link	c.3798G>A	p.Leu1266Leu	synonymous_variant	Exon 5 of 15	5		ENSP00000368755.3		Q9UKN1-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1354

AN:

71398

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0246

Gnomad AMI

AF:

0.0129

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.0172

Gnomad EAS

AF:

0.00456

Gnomad SAS

AF:

0.0159

Gnomad FIN

AF:

0.0122

Gnomad MID

AF:

0.00505

Gnomad NFE

AF:

0.0203

Gnomad OTH

AF:

0.0165

GnomAD3 exomes

AF:

0.00517

AC:

544

AN:

105204

Hom.:

139

AF XY:

0.00558

AC XY:

310

AN XY:

55578

show subpopulations

Gnomad AFR exome

AF:

0.0105

Gnomad AMR exome

AF:

0.00425

Gnomad ASJ exome

AF:

0.00310

Gnomad EAS exome

AF:

0.00685

Gnomad SAS exome

AF:

0.00958

Gnomad FIN exome

AF:

0.000885

Gnomad NFE exome

AF:

0.00351

Gnomad OTH exome

AF:

0.00602

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.468

AC:

463572

AN:

990766

Hom.:

174809

Cov.:

AF XY:

0.460

AC XY:

224614

AN XY:

487998

show subpopulations

Gnomad4 AFR exome

AF:

0.388

Gnomad4 AMR exome

AF:

0.129

Gnomad4 ASJ exome

AF:

0.293

Gnomad4 EAS exome

AF:

0.233

Gnomad4 SAS exome

AF:

0.398

Gnomad4 FIN exome

AF:

0.212

Gnomad4 NFE exome

AF:

0.512

Gnomad4 OTH exome

AF:

0.400

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0189

AC:

1354

AN:

71496

Hom.:

Cov.:

AF XY:

0.0195

AC XY:

680

AN XY:

34946

show subpopulations

Gnomad4 AFR

AF:

0.0245

Gnomad4 AMR

AF:

0.0109

Gnomad4 ASJ

AF:

0.0172

Gnomad4 EAS

AF:

0.00457

Gnomad4 SAS

AF:

0.0159

Gnomad4 FIN

AF:

0.0122

Gnomad4 NFE

AF:

0.0203

Gnomad4 OTH

AF:

0.0161

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.2

DANN

Benign

0.45

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