Genetic Variant NM_001040105.2:c.8950G>A (chr7-101040366-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001040105.2(MUC17):c.8950G>A(p.Glu2984Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,611,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

MUC17
NM_001040105.2 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.0170

Publications

6 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12251407).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC17	NM_001040105.2 link	c.8950G>A	p.Glu2984Lys	missense_variant	Exon 3 of 13	ENST00000306151.9	NP_001035194.1	Q685J3-1
MUC17	NR_133665.2 link	n.9005G>A		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.8950G>A	p.Glu2984Lys	missense_variant	Exon 3 of 13	1	NM_001040105.2	ENSP00000302716.4	Q685J3-1
MUC17	ENST00000379439.3 link	n.8950G>A		non_coding_transcript_exon_variant	Exon 3 of 12	1		ENSP00000368751.3	E7EPM4
MUC12-AS1	ENST00000844128.1 link	n.344+23619C>T		intron_variant	Intron 1 of 1
MUC12-AS1	ENST00000844129.1 link	n.339+23619C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000531

AC:

AN:

150784

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000489

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000737

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000518

AC:

AN:

251096

AF XY:

0.0000590

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000445

AC:

AN:

1461118

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

726850

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44502

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39664

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86194

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000504

AC:

AN:

1111652

Other (OTH)

AF:

0.0000497

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

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

AF:

0.0000531

AC:

AN:

150784

Hom.:

Cov.:

AF XY:

0.0000408

AC XY:

AN XY:

73548

show subpopulations

African (AFR)

AF:

0.0000489

AC:

AN:

40930

American (AMR)

AF:

0.00

AC:

AN:

15042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.000195

AC:

AN:

5128

South Asian (SAS)

AF:

0.00

AC:

AN:

4772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.0000737

AC:

AN:

67808

Other (OTH)

AF:

0.00

AC:

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.0000658

Hom.:

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Prostate cancer

Uncertain:1

Science for Life laboratory, Karolinska Institutet

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.019

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.57

M_CAP

Benign

0.00080

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

0.017

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.49

REVEL

Benign

0.051

Sift

Benign

0.044

Polyphen

0.98

Vest4

0.082

MVP

0.014

ClinPred

0.080

GERP RS

-0.98

Varity_R

0.051

gMVP

0.0070

Mutation Taster

=100/0

polymorphism

(source)

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over