chr7-101058170-T-C

Variant names:

• chr7-101058170-T-C
• rs4729655
• NM_001040105.2:c.*126T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 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)

RN7SKP54 (HGNC:45778): (RN7SK pseudogene 54)

ACMG classification

Our verdict: Benign. The variant received -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.

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.*126T>C		3_prime_UTR	Exon 13 of 13	NP_001035194.1
	MUC17	NR_133665.2		n.13511T>C		non_coding_transcript_exon	Exon 12 of 12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC17	ENST00000306151.9	TSL:1 MANE Select	c.*126T>C		3_prime_UTR	Exon 13 of 13	ENSP00000302716.4
	MUC17	ENST00000379439.3	TSL:1	n.*667T>C		non_coding_transcript_exon	Exon 12 of 12	ENSP00000368751.3
	MUC17	ENST00000379439.3	TSL:1	n.*667T>C		3_prime_UTR	Exon 12 of 12	ENSP00000368751.3

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

African (AFR) AF: 0.293 AC: 4852 AN: 16572

American (AMR) AF: 0.394 AC: 11958 AN: 30328

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 7947 AN: 17780

East Asian (EAS) AF: 0.686 AC: 23290 AN: 33946

South Asian (SAS) AF: 0.587 AC: 34822 AN: 59292

European-Finnish (FIN) AF: 0.506 AC: 23477 AN: 46418

Middle Eastern (MID) AF: 0.376 AC: 1164 AN: 3096

European-Non Finnish (NFE) AF: 0.509 AC: 215312 AN: 422852

Other (OTH) AF: 0.496 AC: 16166 AN: 32570

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

African (AFR) AF: 0.284 AC: 11762 AN: 41466

American (AMR) AF: 0.370 AC: 5648 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1522 AN: 3468

East Asian (EAS) AF: 0.667 AC: 3432 AN: 5142

South Asian (SAS) AF: 0.597 AC: 2875 AN: 4816

European-Finnish (FIN) AF: 0.495 AC: 5218 AN: 10542

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34229 AN: 67964

Other (OTH) AF: 0.421 AC: 888 AN: 2108

Alfa AF: 0.463 Hom.: 8696

Bravo AF: 0.419

Asia WGS AF: 0.638 AC: 2217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.8
DANN	Benign	0.65
PhyloP100		-0.061
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: rs4729655; hg19: chr7-100701451; COSMIC: COSV60285831; COSMIC: COSV60285831;