dbSNP rs10953316: MUC17:p.Thr2355Thr (chr7-101038481-A-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001040105.2(MUC17):c.7065A>C(p.Thr2355Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,554 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MUC17
NM_001040105.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -8.17

Publications

18 publications found

Variant links:

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]

MUC17 links:

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

MUC12-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.2).

BP7

Synonymous conserved (PhyloP=-8.17 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC17	NM_001040105.2 link	c.7065A>C	p.Thr2355Thr	synonymous_variant	Exon 3 of 13	ENST00000306151.9	NP_001035194.1	Q685J3-1
MUC17	NR_133665.2 link	n.7120A>C		non_coding_transcript_exon_variant	Exon 3 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MUC17	ENST00000306151.9 link	c.7065A>C	p.Thr2355Thr	synonymous_variant	Exon 3 of 13	1	NM_001040105.2	ENSP00000302716.4	Q685J3-1
MUC17	ENST00000379439.3 link	n.7065A>C		non_coding_transcript_exon_variant	Exon 3 of 12	1		ENSP00000368751.3	E7EPM4
MUC12-AS1	ENST00000844128.1 link	n.345-24042T>G		intron_variant	Intron 1 of 1
MUC12-AS1	ENST00000844129.1 link	n.340-23214T>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251252

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461554

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727070

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1111774

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000132

AC:

AN:

151248

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73844

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41244

American (AMR)

AF:

0.00

AC:

AN:

15104

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10472

Middle Eastern (MID)

AF:

0.00

AC:

AN:

300

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67730

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

11118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.2

CADD

Benign

0.34

(source)

DANN

Benign

0.11

PhyloP100

-8.2

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over