7-101004267-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001164462.2(MUC12):​c.13704G>T​(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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency:
  • Genomes: not found (cov: 3)
  • Exomes 𝑓: 0.0000019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC12 NM_001164462.2 missense
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05076474).

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

Frequencies

GnomAD3 genomes Cov.: 3

GnomAD2 exomes AF: 0.0000165 AC: 1 AN: 60668 AF XY: 0.0000328

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000186 AC: 1 AN: 537444 Hom.: 0 Cov.: 8 AF XY: 0.00000367 AC XY: 1 AN XY: 272338

African (AFR) AF: 0.00 AC: 0 AN: 14138

American (AMR) AF: 0.00 AC: 0 AN: 17562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13214

East Asian (EAS) AF: 0.00 AC: 0 AN: 26706

South Asian (SAS) AF: 0.0000280 AC: 1 AN: 35662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2048

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 375692

Other (OTH) AF: 0.00 AC: 0 AN: 27446

GnomAD4 genome Cov.: 3

Alfa AF: 0.00 Hom.: 422

ExAC AF: 0.000252 AC: 2

ClinVar

Not reported in ClinVar

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	0.13
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.3
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.014
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.057	T
Vest4		0.011
MutPred		0.12		Gain of phosphorylation at T4566 (P = 0.13)
MVP		0.014
ClinPred		0.055	T
GERP RS		-1.8
Varity_R		0.043
gMVP		0.0012
Mutation Taster		=100/0	polymorphism

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;