7-101038481-A-G

Position:

• chr7-101038481-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001040105.2(MUC17):​c.7065A>G​(p.Thr2355=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 1,612,820 control chromosomes in the GnomAD database, including 330,663 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.67 (34610 hom., cov: 32)
  • Exomes 𝑓: 0.63 (296053 hom.)
• Consequence: MUC17 NM_001040105.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -8.17

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.15).
• BP7: Synonymous conserved (PhyloP=-8.17 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC17	NM_001040105.2	c.7065A>G	p.Thr2355=	synonymous_variant	3/13	ENST00000306151.9
MUC17	NR_133665.2	n.7120A>G		non_coding_transcript_exon_variant	3/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC17	ENST00000306151.9	c.7065A>G	p.Thr2355=	synonymous_variant	3/13	1	NM_001040105.2	P1
MUC17	ENST00000379439.3	c.7065A>G	p.Thr2355=	synonymous_variant, NMD_transcript_variant	3/12	1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101309 AN: 151192 Hom.: 34567 Cov.: 32

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.577

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.644

GnomAD3 exomes AF: 0.640 AC: 160704 AN: 251252 Hom.: 52576 AF XY: 0.645 AC XY: 87518 AN XY: 135772

Gnomad AFR exome AF: 0.793

Gnomad AMR exome AF: 0.499

Gnomad ASJ exome AF: 0.632

Gnomad EAS exome AF: 0.806

Gnomad SAS exome AF: 0.731

Gnomad FIN exome AF: 0.610

Gnomad NFE exome AF: 0.616

Gnomad OTH exome AF: 0.630

GnomAD4 exome AF: 0.634 AC: 925952 AN: 1461506 Hom.: 296053 Cov.: 68 AF XY: 0.637 AC XY: 462968 AN XY: 727050

Gnomad4 AFR exome AF: 0.803

Gnomad4 AMR exome AF: 0.501

Gnomad4 ASJ exome AF: 0.626

Gnomad4 EAS exome AF: 0.797

Gnomad4 SAS exome AF: 0.727

Gnomad4 FIN exome AF: 0.607

Gnomad4 NFE exome AF: 0.621

Gnomad4 OTH exome AF: 0.654

GnomAD4 genome AF: 0.670 AC: 101400 AN: 151314 Hom.: 34610 Cov.: 32 AF XY: 0.667 AC XY: 49331 AN XY: 73948

Gnomad4 AFR AF: 0.792

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.647

Alfa AF: 0.623 Hom.: 11118

Bravo AF: 0.667

Asia WGS AF: 0.797 AC: 2770 AN: 3478

EpiCase AF: 0.628

EpiControl AF: 0.626

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.39
DANN	Benign	0.10

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

Publications

LitVar

Other links and lift over

dbSNP: rs10953316; hg19: chr7-100681762; COSMIC: COSV60281906;