rs79635145

Variant names:

• chr7-101004258-C-T
• rs79635145
• NM_001164462.2:c.13695C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001164462.2(MUC12):​c.13695C>T​(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. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (473 hom., cov: 3)
  • Exomes 𝑓: 0.64 (83552 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC12 NM_001164462.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.91
• Publications: 2 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 7-101004258-C-T is Benign according to our data. Variant chr7-101004258-C-T is described in ClinVar as Benign. ClinVar VariationId is 403116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC12	NM_001164462.2	MANE Select	c.13695C>T	p.Ser4565Ser	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.13695C>T	p.Ser4565Ser	synonymous	Exon 2 of 12	ENSP00000441929.1
	MUC12	ENST00000379442.7	TSL:5	c.14124C>T	p.Ser4708Ser	synonymous	Exon 5 of 15	ENSP00000368755.3

Frequencies

GnomAD3 genomes AF: 0.571 AC: 1191 AN: 2086 Hom.: 473 Cov.: 3

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.636

GnomAD2 exomes AF: 0.751 AC: 40691 AN: 54170 AF XY: 0.752

Gnomad AFR exome AF: 0.736

Gnomad AMR exome AF: 0.792

Gnomad ASJ exome AF: 0.744

Gnomad EAS exome AF: 0.815

Gnomad FIN exome AF: 0.684

Gnomad NFE exome AF: 0.723

Gnomad OTH exome AF: 0.761

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.636 AC: 283155 AN: 445316 Hom.: 83552 Cov.: 7 AF XY: 0.636 AC XY: 143557 AN XY: 225548

African (AFR) AF: 0.671 AC: 8409 AN: 12538

American (AMR) AF: 0.740 AC: 10375 AN: 14014

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 7835 AN: 11636

East Asian (EAS) AF: 0.773 AC: 19178 AN: 24800

South Asian (SAS) AF: 0.611 AC: 15623 AN: 25588

European-Finnish (FIN) AF: 0.636 AC: 13871 AN: 21816

Middle Eastern (MID) AF: 0.718 AC: 1263 AN: 1760

European-Non Finnish (NFE) AF: 0.617 AC: 190958 AN: 309550

Other (OTH) AF: 0.662 AC: 15643 AN: 23614

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.572 AC: 1193 AN: 2084 Hom.: 473 Cov.: 3 AF XY: 0.563 AC XY: 526 AN XY: 934

African (AFR) AF: 0.585 AC: 242 AN: 414

American (AMR) AF: 0.695 AC: 132 AN: 190

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 39 AN: 64

East Asian (EAS) AF: 0.778 AC: 56 AN: 72

South Asian (SAS) AF: 0.653 AC: 47 AN: 72

European-Finnish (FIN) AF: 0.500 AC: 123 AN: 246

Middle Eastern (MID) AF: 0.500 AC: 3 AN: 6

European-Non Finnish (NFE) AF: 0.538 AC: 526 AN: 978

Other (OTH) AF: 0.625 AC: 15 AN: 24

Alfa AF: 0.711 Hom.: 3380

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.19
PhyloP100		-3.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs79635145; hg19: chr7-100647539; COSMIC: COSV65183822;