rs752727121

Variant names:

• chr7-100991613-G-A
• rs752727121
• NM_001164462.2:c.1050G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-100991613-G-A
• chr7-100991613-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001164462.2(MUC12):​c.1050G>A​(p.Ala350Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000425 in 1,302,494 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00089 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00043 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC12 NM_001164462.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.42

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 7-100991613-G-A is Benign according to our data. Variant chr7-100991613-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3770855.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.42 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC12	NM_001164462.2	c.1050G>A	p.Ala350Ala	synonymous_variant	Exon 2 of 12	ENST00000536621.6	NP_001157934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC12	ENST00000536621.6	c.1050G>A	p.Ala350Ala	synonymous_variant	Exon 2 of 12	5	NM_001164462.2	ENSP00000441929.1
MUC12	ENST00000379442.7	c.1479G>A	p.Ala493Ala	synonymous_variant	Exon 5 of 15	5		ENSP00000368755.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 86 AN: 96352 Hom.: 0 Cov.: 28 FAILED QC

Gnomad AFR AF: 0.000191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000291

Gnomad ASJ AF: 0.00411

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000370

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.00171

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000425 AC: 554 AN: 1302494 Hom.: 2 Cov.: 124 AF XY: 0.000478 AC XY: 306 AN XY: 640142

Gnomad4 AFR exome AF: 0.0000650

Gnomad4 AMR exome AF: 0.000297

Gnomad4 ASJ exome AF: 0.00212

Gnomad4 EAS exome AF: 0.000166

Gnomad4 SAS exome AF: 0.000526

Gnomad4 FIN exome AF: 0.000135

Gnomad4 NFE exome AF: 0.000387

Gnomad4 OTH exome AF: 0.000899

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000892 AC: 86 AN: 96464 Hom.: 0 Cov.: 28 AF XY: 0.000759 AC XY: 36 AN XY: 47418

Gnomad4 AFR AF: 0.000191

Gnomad4 AMR AF: 0.000291

Gnomad4 ASJ AF: 0.00411

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000371

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00171

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0998 Hom.: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MUC12: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.76
DANN	Benign	0.40

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

Other links and lift over

dbSNP: rs752727121; hg19: chr7-100634894; COSMIC: COSV65182850;