rs114626579

Variant names:

• chr20-62956895-A-G
• rs114626579
• NM_022082.4:c.190A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-62956895-A-G
• chr20-62956895-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022082.4(SLC17A9):​c.190A>G​(p.Ile64Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,318 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I64F) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC17A9 NM_022082.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.451

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058672726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A9	NM_022082.4	c.190A>G	p.Ile64Val	missense_variant	Exon 2 of 13	ENST00000370351.9	NP_071365.4
SLC17A9	NM_001302643.2	c.172A>G	p.Ile58Val	missense_variant	Exon 3 of 14		NP_001289572.2
SLC17A9	XM_011528978.3	c.-145A>G		5_prime_UTR_variant	Exon 1 of 12		XP_011527280.1
SLC17A9	XR_936601.4	n.312A>G		non_coding_transcript_exon_variant	Exon 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A9	ENST00000370351.9	c.190A>G	p.Ile64Val	missense_variant	Exon 2 of 13	1	NM_022082.4	ENSP00000359376.4
SLC17A9	ENST00000370349.7	c.172A>G	p.Ile58Val	missense_variant	Exon 3 of 14	1		ENSP00000359374.3
SLC17A9	ENST00000411611.1	c.250A>G	p.Ile84Val	missense_variant	Exon 2 of 3	2		ENSP00000388215.1
SLC17A9	ENST00000488738.5	n.310A>G		non_coding_transcript_exon_variant	Exon 2 of 11	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461318 Hom.: 0 Cov.: 79 AF XY: 0.00 AC XY: 0 AN XY: 726978

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.0060
DANN	Benign	0.30
DEOGEN2	Benign	0.083	T;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.059	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.065	N;.;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.040	N;N;N
REVEL	Benign	0.084
Sift	Benign	0.71	T;T;T
Sift4G	Benign	0.77	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.083
MutPred		0.54		Gain of catalytic residue at I64 (P = 0.0084);.;.;
MVP		0.030
MPC		0.36
ClinPred		0.031	T
GERP RS		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.016
gMVP		0.093

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

Other links and lift over

dbSNP: rs114626579; hg19: chr20-61588247;