NM_001164462.2:c.1050G>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001164462.2(MUC12):​c.1050G>T​(p.Ala350Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000766 in 1,304,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A350A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: MUC12 NM_001164462.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.42
• Publications: 0 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP7: Synonymous conserved (PhyloP=-3.42 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC12	NM_001164462.2	MANE Select	c.1050G>T	p.Ala350Ala	synonymous	Exon 2 of 12	NP_001157934.1	Q9UKN1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC12	ENST00000536621.6	TSL:5 MANE Select	c.1050G>T	p.Ala350Ala	synonymous	Exon 2 of 12	ENSP00000441929.1	Q9UKN1-2
	MUC12	ENST00000379442.7	TSL:5	c.1479G>T	p.Ala493Ala	synonymous	Exon 5 of 15	ENSP00000368755.3	Q9UKN1-1
	MUC12	ENST00000895813.1		c.68-14858G>T		intron	N/A	ENSP00000565872.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 7.66e-7 AC: 1 AN: 1304750 Hom.: 0 Cov.: 124 AF XY: 0.00000156 AC XY: 1 AN XY: 641310

African (AFR) AF: 0.00 AC: 0 AN: 30770

American (AMR) AF: 0.00 AC: 0 AN: 33744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22218

East Asian (EAS) AF: 0.00 AC: 0 AN: 30276

South Asian (SAS) AF: 0.00 AC: 0 AN: 72534

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5376

European-Non Finnish (NFE) AF: 9.74e-7 AC: 1 AN: 1026672

Other (OTH) AF: 0.00 AC: 0 AN: 53494

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.16
DANN	Benign	0.38
PhyloP100		-3.4

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: rs752727121; hg19: chr7-100634894;