7-101058170-T-C

Position:

• chr7-101058170-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040105.2(MUC17):​c.*126T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 814,832 control chromosomes in the GnomAD database, including 102,982 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 0.44 (15396 hom., cov: 31)
  • Exomes 𝑓: 0.51 (87586 hom.)
• Consequence: MUC17 NM_001040105.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC17	NM_001040105.2	c.*126T>C		3_prime_UTR_variant	13/13	ENST00000306151.9
MUC17	NR_133665.2	n.13511T>C		non_coding_transcript_exon_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC17	ENST00000306151.9	c.*126T>C		3_prime_UTR_variant	13/13	1	NM_001040105.2	P1
MUC17	ENST00000379439.3	c.*667T>C		3_prime_UTR_variant, NMD_transcript_variant	12/12	1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66172 AN: 151860 Hom.: 15403 Cov.: 31

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.421

GnomAD4 exome AF: 0.511 AC: 338988 AN: 662854 Hom.: 87586 Cov.: 9 AF XY: 0.515 AC XY: 180176 AN XY: 349754

Gnomad4 AFR exome AF: 0.293

Gnomad4 AMR exome AF: 0.394

Gnomad4 ASJ exome AF: 0.447

Gnomad4 EAS exome AF: 0.686

Gnomad4 SAS exome AF: 0.587

Gnomad4 FIN exome AF: 0.506

Gnomad4 NFE exome AF: 0.509

Gnomad4 OTH exome AF: 0.496

GnomAD4 genome AF: 0.435 AC: 66172 AN: 151978 Hom.: 15396 Cov.: 31 AF XY: 0.434 AC XY: 32249 AN XY: 74264

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.421

Alfa AF: 0.456 Hom.: 5670

Bravo AF: 0.419

Asia WGS AF: 0.638 AC: 2217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.8
DANN	Benign	0.65

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: rs4729655; hg19: chr7-100701451; COSMIC: COSV60285831; COSMIC: COSV60285831;