20-62956892-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_022082.4(SLC17A9):c.187G>A(p.Gly63Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000126 in 1,613,654 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00013 ( 3 hom. )

Consequence

SLC17A9
NM_022082.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.15

Publications

2 publications found

Variant links:

Genes affected

SLC17A9 (HGNC:16192): (solute carrier family 17 member 9) This gene encodes a member of a family of transmembrane proteins that are involved in the transport of small molecules. The encoded protein participates in the vesicular uptake, storage, and secretion of adenoside triphosphate (ATP) and other nucleotides. A mutation in this gene was found in individuals with autosomal dominant disseminated superficial actinic porokeratosis-8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

SLC17A9 Gene-Disease associations (from GenCC):

disseminated superficial actinic porokeratosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
porokeratosis 8, disseminated superficial actinic type
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

SLC17A9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PP3

MetaRNN computational evidence supports a deleterious effect, 0.832

BS2

High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A9	NM_022082.4 link	c.187G>A	p.Gly63Ser	missense_variant	Exon 2 of 13	ENST00000370351.9	NP_071365.4	Q9BYT1-1
SLC17A9	NM_001302643.2 link	c.169G>A	p.Gly57Ser	missense_variant	Exon 3 of 14		NP_001289572.2	Q9BYT1-2H0UI90
SLC17A9	XR_936601.4 link	n.309G>A		non_coding_transcript_exon_variant	Exon 2 of 10
SLC17A9	XM_011528978.3 link	c.-148G>A		5_prime_UTR_variant	Exon 1 of 12		XP_011527280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC17A9	ENST00000370351.9 link	c.187G>A	p.Gly63Ser	missense_variant	Exon 2 of 13	1	NM_022082.4	ENSP00000359376.4	Q9BYT1-1
SLC17A9	ENST00000370349.7 link	c.169G>A	p.Gly57Ser	missense_variant	Exon 3 of 14	1		ENSP00000359374.3	Q9BYT1-2
SLC17A9	ENST00000411611.1 link	c.247G>A	p.Gly83Ser	missense_variant	Exon 2 of 3	2		ENSP00000388215.1	Q5W197
SLC17A9	ENST00000488738.5 link	n.307G>A		non_coding_transcript_exon_variant	Exon 2 of 11	2

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000178

AC:

AN:

247750

AF XY:

0.000208

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000985

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000127

AC:

186

AN:

1461310

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

113

AN XY:

726972

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33480

American (AMR)

AF:

0.000246

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000939

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52872

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000728

AC:

AN:

1111998

Other (OTH)

AF:

0.000116

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000112

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41582

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00145

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.000106

ESP6500AA

AF:

0.000235

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000140

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.187G>A (p.G63S) alteration is located in exon 2 (coding exon 2) of the SLC17A9 gene. This alteration results from a G to A substitution at nucleotide position 187, causing the glycine (G) at amino acid position 63 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Uncertain

0.090

BayesDel_noAF

Pathogenic

0.26

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

D;.;.

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Uncertain

0.19

MetaRNN

Pathogenic

0.83

D;D;D

MetaSVM

Uncertain

-0.062

MutationAssessor

Uncertain

2.8

M;.;.

PhyloP100

7.1

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-5.7

D;D;D

REVEL

Pathogenic

0.72

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.054

T;T;T

Polyphen

1.0

D;D;.

Vest4

0.96

MVP

0.48

MPC

1.3

ClinPred

0.81

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.89

gMVP

0.77

Mutation Taster

=89/11

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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20-62956892-G-A

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