NM_001164462.2:c.3369G>C

Variant names:

• chr7-100993932-G-C
• rs76022775
• NM_001164462.2:c.3369G>C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001164462.2(MUC12):​c.3369G>C​(p.Leu1123Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000404 in 1,212,110 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.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 13)
  • Exomes 𝑓: 0.000040 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC12 NM_001164462.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• 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	c.3369G>C	p.Leu1123Leu	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.3369G>C	p.Leu1123Leu	synonymous_variant	Exon 2 of 12	5	NM_001164462.2	ENSP00000441929.1
MUC12	ENST00000379442.7	c.3798G>C	p.Leu1266Leu	synonymous_variant	Exon 5 of 15	5		ENSP00000368755.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 74118 Hom.: 0 Cov.: 13 FAILED QC

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 AF: 0.0000404 AC: 49 AN: 1212110 Hom.: 0 Cov.: 78 AF XY: 0.0000403 AC XY: 24 AN XY: 595286

Gnomad4 AFR exome AF: 0.000111

Gnomad4 AMR exome AF: 0.000195

Gnomad4 ASJ exome AF: 0.000193

Gnomad4 EAS exome AF: 0.000115

Gnomad4 SAS exome AF: 0.0000573

Gnomad4 FIN exome AF: 0.0000390

Gnomad4 NFE exome AF: 0.0000282

Gnomad4 OTH exome AF: 0.0000204

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 74218 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 36328

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.96
DANN	Benign	0.39

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: rs76022775; hg19: chr7-100637213;