7-101004258-C-A

Variant names:

• chr7-101004258-C-A
• NM_001164462.2:c.13695C>A
• MUC12 p.Ser4565Ser

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.13695C>A​(p.Ser4565Ser) 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. Synonymous variant affecting the same amino acid position (i.e. S4565S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 3)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC12 NM_001164462.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.91
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP7: Synonymous conserved (PhyloP=-3.91 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.13695C>A	p.Ser4565Ser	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.13695C>A	p.Ser4565Ser	synonymous	Exon 2 of 12	ENSP00000441929.1	Q9UKN1-2
	MUC12	ENST00000379442.7	TSL:5	c.14124C>A	p.Ser4708Ser	synonymous	Exon 5 of 15	ENSP00000368755.3	Q9UKN1-1
	MUC12	ENST00000895813.1		c.68-2213C>A		intron	N/A	ENSP00000565872.1

Frequencies

GnomAD3 genomes Cov.: 3

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 447874 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 226812

African (AFR) AF: 0.00 AC: 0 AN: 12598

American (AMR) AF: 0.00 AC: 0 AN: 14048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11658

East Asian (EAS) AF: 0.00 AC: 0 AN: 24844

South Asian (SAS) AF: 0.00 AC: 0 AN: 25706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 311622

Other (OTH) AF: 0.00 AC: 0 AN: 23744

GnomAD4 genome Cov.: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.19
PhyloP100		-3.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-100647539;