20-62962631-C-G

Position:

chr20-62962631-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_022082.4(SLC17A9):c.505C>G(p.Leu169Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SLC17A9
NM_022082.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.04

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07905531).

BP6

Variant 20-62962631-C-G is Benign according to our data. Variant chr20-62962631-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2468181.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC17A9	NM_022082.4 linkuse as main transcript	c.505C>G	p.Leu169Val	missense_variant	5/13	ENST00000370351.9	NP_071365.4
SLC17A9	NM_001302643.2 linkuse as main transcript	c.487C>G	p.Leu163Val	missense_variant	6/14		NP_001289572.2
SLC17A9	XM_011528978.3 linkuse as main transcript	c.145C>G	p.Leu49Val	missense_variant	4/12		XP_011527280.1
SLC17A9	XR_936601.4 linkuse as main transcript	n.627C>G		non_coding_transcript_exon_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC17A9	ENST00000370351.9 linkuse as main transcript	c.505C>G	p.Leu169Val	missense_variant	5/13	1	NM_022082.4	ENSP00000359376	P1	Q9BYT1-1
SLC17A9	ENST00000370349.7 linkuse as main transcript	c.487C>G	p.Leu163Val	missense_variant	6/14	1		ENSP00000359374		Q9BYT1-2
SLC17A9	ENST00000459704.6 linkuse as main transcript	n.132C>G		non_coding_transcript_exon_variant	2/10	3
SLC17A9	ENST00000488738.5 linkuse as main transcript	n.625C>G		non_coding_transcript_exon_variant	5/11	2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152252

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248960

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135134

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461506

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727074

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000242

AC:

ExAC

AF:

0.00000827

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.5

DANN

Benign

0.70

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.0095

MetaRNN

Benign

0.079

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.49

N;.

MutationTaster

Benign

0.94

D;D

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.075

Sift

Benign

0.46

T;T

Sift4G

Benign

0.52

T;T

Polyphen

0.013

B;B

Vest4

0.23

MVP

0.040

MPC

0.44

ClinPred

0.050

GERP RS

0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.042

gMVP

0.22

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over