chr20-62957451-G-A

Position:

chr20-62957451-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The ENST00000370351.9(SLC17A9):c.268G>A(p.Glu90Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000691 in 1,591,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

SLC17A9
ENST00000370351.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.12

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.38980424).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC17A9	NM_022082.4 linkuse as main transcript	c.268G>A	p.Glu90Lys	missense_variant	3/13	ENST00000370351.9	NP_071365.4
SLC17A9	NM_001302643.2 linkuse as main transcript	c.250G>A	p.Glu84Lys	missense_variant	4/14		NP_001289572.2
SLC17A9	XM_011528978.3 linkuse as main transcript	c.-93G>A		5_prime_UTR_variant	2/12		XP_011527280.1
SLC17A9	XR_936601.4 linkuse as main transcript	n.390G>A		non_coding_transcript_exon_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC17A9	ENST00000370351.9 linkuse as main transcript	c.268G>A	p.Glu90Lys	missense_variant	3/13	1	NM_022082.4	ENSP00000359376	P1	Q9BYT1-1
SLC17A9	ENST00000370349.7 linkuse as main transcript	c.250G>A	p.Glu84Lys	missense_variant	4/14	1		ENSP00000359374		Q9BYT1-2
SLC17A9	ENST00000411611.1 linkuse as main transcript	c.328G>A	p.Glu110Lys	missense_variant	3/3	2		ENSP00000388215
SLC17A9	ENST00000488738.5 linkuse as main transcript	n.388G>A		non_coding_transcript_exon_variant	3/11	2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000177

AC:

AN:

226284

Hom.:

AF XY:

0.00000815

AC XY:

AN XY:

122682

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000128

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000486

AC:

AN:

1438956

Hom.:

Cov.:

AF XY:

0.00000700

AC XY:

AN XY:

714642

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000121

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:

0.00000182

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 02, 2022

The c.268G>A (p.E90K) alteration is located in exon 3 (coding exon 3) of the SLC17A9 gene. This alteration results from a G to A substitution at nucleotide position 268, causing the glutamic acid (E) at amino acid position 90 to be replaced by a lysine (K). 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

Benign

0.31

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.44

T;.;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.067

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.71

N;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.0090

D;D;D

Sift4G

Uncertain

0.050

T;T;T

Polyphen

0.99

D;D;.

Vest4

0.72

MutPred

0.51

Gain of methylation at E90 (P = 0.016);.;.;

MVP

0.36

MPC

1.3

ClinPred

0.66

GERP RS

4.6

Varity_R

0.71

gMVP

0.45

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