7-101031877-A-G

Variant names:

• chr7-101031877-A-G
• NM_001040105.2:c.461A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040105.2(MUC17):​c.461A>G​(p.Glu154Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MUC17 NM_001040105.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.21
• Publications: 0 publications found

Genes affected

MUC17 (HGNC:16800): (mucin 17, cell surface associated) The protein encoded by this gene is a membrane-bound mucin that provides protection to gut epithelial cells. The encoded protein contains about 60 tandem repeats, with each repeat being around 60 aa. N-glycosylation enables the encoded protein to localize on the cell surface, while the C-terminus interacts with the scaffold protein PDZ domain containing 1 (PDZK1). Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Nov 2015]

MUC12-AS1 (HGNC:40382): (MUC12 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.076544434).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040105.2. 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
	MUC17	NM_001040105.2	MANE Select	c.461A>G	p.Glu154Gly	missense	Exon 3 of 13	NP_001035194.1	Q685J3-1
	MUC17	NR_133665.2		n.516A>G		non_coding_transcript_exon	Exon 3 of 12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC17	ENST00000306151.9	TSL:1 MANE Select	c.461A>G	p.Glu154Gly	missense	Exon 3 of 13	ENSP00000302716.4	Q685J3-1
	MUC17	ENST00000379439.3	TSL:1	n.461A>G		non_coding_transcript_exon	Exon 3 of 12	ENSP00000368751.3	E7EPM4
	MUC12-AS1	ENST00000844128.1		n.345-17438T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.0
DANN	Benign	0.63
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.55	N
PhyloP100		-1.2
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.021
Sift	Pathogenic	0.0	D
Polyphen		0.78	P
Vest4		0.035
MutPred		0.14		Gain of glycosylation at S153 (P = 0.0382)
MVP		0.085
ClinPred		0.10	T
GERP RS		-0.89
Varity_R		0.035
gMVP		0.0040
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

hg19: chr7-100675158;