chr7-101004267-G-C

Variant names:

• chr7-101004267-G-C
• rs73402837
• NM_001164462.2:c.13704G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001164462.2(MUC12):​c.13704G>C​(p.Leu4568Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (1120 hom., cov: 3)
  • Exomes 𝑓: 0.64 (102340 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC12 NM_001164462.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.33
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.3845177E-4).
• BP6: Variant 7-101004267-G-C is Benign according to our data. Variant chr7-101004267-G-C is described in ClinVar as Benign. ClinVar VariationId is 403117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.13704G>C	p.Leu4568Phe	missense	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.13704G>C	p.Leu4568Phe	missense	Exon 2 of 12	ENSP00000441929.1
	MUC12	ENST00000379442.7	TSL:5	c.14133G>C	p.Leu4711Phe	missense	Exon 5 of 15	ENSP00000368755.3
	MUC12	ENST00000895813.1		c.68-2204G>C		intron	N/A	ENSP00000565872.1

Frequencies

GnomAD3 genomes AF: 0.652 AC: 2752 AN: 4222 Hom.: 1116 Cov.: 3

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.714

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.705

GnomAD2 exomes AF: 0.757 AC: 45942 AN: 60668 AF XY: 0.755

Gnomad AFR exome AF: 0.800

Gnomad AMR exome AF: 0.792

Gnomad ASJ exome AF: 0.743

Gnomad EAS exome AF: 0.816

Gnomad FIN exome AF: 0.670

Gnomad NFE exome AF: 0.725

Gnomad OTH exome AF: 0.766

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.640 AC: 341410 AN: 533038 Hom.: 102340 Cov.: 8 AF XY: 0.641 AC XY: 173015 AN XY: 270062

African (AFR) AF: 0.720 AC: 10138 AN: 14074

American (AMR) AF: 0.742 AC: 12949 AN: 17442

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 8856 AN: 13134

East Asian (EAS) AF: 0.780 AC: 20776 AN: 26650

South Asian (SAS) AF: 0.608 AC: 21392 AN: 35158

European-Finnish (FIN) AF: 0.635 AC: 15761 AN: 24806

Middle Eastern (MID) AF: 0.724 AC: 1475 AN: 2038

European-Non Finnish (NFE) AF: 0.622 AC: 231850 AN: 372498

Other (OTH) AF: 0.669 AC: 18213 AN: 27238

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.652 AC: 2766 AN: 4242 Hom.: 1120 Cov.: 3 AF XY: 0.651 AC XY: 1222 AN XY: 1876

African (AFR) AF: 0.681 AC: 546 AN: 802

American (AMR) AF: 0.737 AC: 280 AN: 380

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 93 AN: 130

East Asian (EAS) AF: 0.812 AC: 112 AN: 138

South Asian (SAS) AF: 0.664 AC: 101 AN: 152

European-Finnish (FIN) AF: 0.597 AC: 264 AN: 442

Middle Eastern (MID) AF: 0.714 AC: 10 AN: 14

European-Non Finnish (NFE) AF: 0.620 AC: 1310 AN: 2114

Other (OTH) AF: 0.682 AC: 30 AN: 44

Alfa AF: 0.474 Hom.: 422

ExAC AF: 0.468 AC: 3710

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
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.15
DANN	Benign	0.12
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00043	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.00044	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.3
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.031
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.057	T
Vest4		0.011
MutPred		0.12		Gain of phosphorylation at T4566 (P = 0.13)
ClinPred		0.0054	T
GERP RS		-1.8
Varity_R		0.043
gMVP		0.0012
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: rs73402837; hg19: chr7-100647548; COSMIC: COSV65183830;