rs11766125

Variant names:

• chr7-101004836-C-A
• NM_001164462.2:c.14273C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-101004836-C-A
• chr7-101004836-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001164462.2(MUC12):​c.14273C>A​(p.Thr4758Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,385,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: MUC12 NM_001164462.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.604

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054237217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC12	NM_001164462.2	c.14273C>A	p.Thr4758Lys	missense_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.14273C>A	p.Thr4758Lys	missense_variant	Exon 2 of 12	5	NM_001164462.2	ENSP00000441929.1
MUC12	ENST00000379442.7	c.14702C>A	p.Thr4901Lys	missense_variant	Exon 5 of 15	5		ENSP00000368755.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1385580 Hom.: 0 Cov.: 78 AF XY: 0.00000146 AC XY: 1 AN XY: 683682

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.3
DANN	Benign	0.28
DEOGEN2	Benign	0.050	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.20	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.014
Sift	Benign	0.29	T;T
Sift4G	Uncertain	0.050	T;T
Vest4		0.039
MutPred		0.19		.;Gain of ubiquitination at T4758 (P = 0.0054);
MVP		0.030
ClinPred		0.072	T
GERP RS		-0.98
Varity_R		0.088
gMVP		0.022

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-100648117;