rs73402837

Variant names:

• chr7-101004267-G-A
• rs73402837
• NM_001164462.2:c.13704G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-101004267-G-A
• chr7-101004267-G-C
• chr7-101004267-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001164462.2(MUC12):​c.13704G>A​(p.Leu4568Leu) 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 0.0 (0 hom., cov: 3)
  • Exomes 𝑓: 0.0000019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC12 NM_001164462.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 4 publications found

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP7: Synonymous conserved (PhyloP=-1.34 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC12	NM_001164462.2	MANE Select	c.13704G>A	p.Leu4568Leu	synonymous	Exon 2 of 12	NP_001157934.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC12	ENST00000536621.6	TSL:5 MANE Select	c.13704G>A	p.Leu4568Leu	synonymous	Exon 2 of 12	ENSP00000441929.1
	MUC12	ENST00000379442.7	TSL:5	c.14133G>A	p.Leu4711Leu	synonymous	Exon 5 of 15	ENSP00000368755.3
	MUC12	ENST00000895813.1		c.68-2204G>A		intron	N/A	ENSP00000565872.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 4224 Hom.: 0 Cov.: 3

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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00000186 AC: 1 AN: 537448 Hom.: 0 Cov.: 8 AF XY: 0.00000367 AC XY: 1 AN XY: 272340

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 14138

American (AMR) AF: 0.00 AC: 0 AN: 17560

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13214

East Asian (EAS) AF: 0.0000374 AC: 1 AN: 26706

South Asian (SAS) AF: 0.00 AC: 0 AN: 35662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2048

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 375696

Other (OTH) AF: 0.00 AC: 0 AN: 27448

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4224 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 1856

African (AFR) AF: 0.00 AC: 0 AN: 788

American (AMR) AF: 0.00 AC: 0 AN: 374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 130

East Asian (EAS) AF: 0.00 AC: 0 AN: 136

South Asian (SAS) AF: 0.00 AC: 0 AN: 156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 14

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2112

Other (OTH) AF: 0.00 AC: 0 AN: 44

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.38
DANN	Benign	0.35
PhyloP100		-1.3

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

Other links and lift over

dbSNP: rs73402837; hg19: chr7-100647548;