7-101038481-A-G

Variant names:

• chr7-101038481-A-G
• rs10953316
• NM_001040105.2:c.7065A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001040105.2(MUC17):​c.7065A>G​(p.Thr2355Thr) 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
• Publications: 18 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
MUC17	NM_001040105.2	c.7065A>G	p.Thr2355Thr	synonymous_variant	Exon 3 of 13	ENST00000306151.9	NP_001035194.1
MUC17	NR_133665.2	n.7120A>G		non_coding_transcript_exon_variant	Exon 3 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC17	ENST00000306151.9	c.7065A>G	p.Thr2355Thr	synonymous_variant	Exon 3 of 13	1	NM_001040105.2	ENSP00000302716.4
MUC17	ENST00000379439.3	n.7065A>G		non_coding_transcript_exon_variant	Exon 3 of 12	1		ENSP00000368751.3
MUC12-AS1	ENST00000844128.1	n.345-24042T>C		intron_variant	Intron 1 of 1
MUC12-AS1	ENST00000844129.1	n.340-23214T>C		intron_variant	Intron 1 of 2

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

GnomAD2 exomes AF: 0.640 AC: 160704 AN: 251252 AF XY: 0.645

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 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

African (AFR) AF: 0.803 AC: 26874 AN: 33474

American (AMR) AF: 0.501 AC: 22382 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 16363 AN: 26126

East Asian (EAS) AF: 0.797 AC: 31625 AN: 39690

South Asian (SAS) AF: 0.727 AC: 62726 AN: 86236

European-Finnish (FIN) AF: 0.607 AC: 32438 AN: 53402

Middle Eastern (MID) AF: 0.599 AC: 3453 AN: 5768

European-Non Finnish (NFE) AF: 0.621 AC: 690617 AN: 1111732

Other (OTH) AF: 0.654 AC: 39474 AN: 60380

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

African (AFR) AF: 0.792 AC: 32737 AN: 41338

American (AMR) AF: 0.518 AC: 7833 AN: 15118

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2180 AN: 3460

East Asian (EAS) AF: 0.807 AC: 4143 AN: 5134

South Asian (SAS) AF: 0.751 AC: 3607 AN: 4802

European-Finnish (FIN) AF: 0.606 AC: 6347 AN: 10470

Middle Eastern (MID) AF: 0.557 AC: 157 AN: 282

European-Non Finnish (NFE) AF: 0.626 AC: 42402 AN: 67708

Other (OTH) AF: 0.647 AC: 1358 AN: 2100

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
PhyloP100		-8.2
Mutation Taster		=99/1	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: rs10953316; hg19: chr7-100681762; COSMIC: COSV60281906;