20-62957490-A-G

Variant names:

• chr20-62957490-A-G
• rs1033287330
• NM_022082.4:c.307A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_022082.4(SLC17A9):​c.307A>G​(p.Ile103Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,457,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SLC17A9 NM_022082.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.842
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22017968).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A9	NM_022082.4	c.307A>G	p.Ile103Val	missense_variant	Exon 3 of 13	ENST00000370351.9	NP_071365.4
SLC17A9	NM_001302643.2	c.289A>G	p.Ile97Val	missense_variant	Exon 4 of 14		NP_001289572.2
SLC17A9	XR_936601.4	n.429A>G		non_coding_transcript_exon_variant	Exon 3 of 10
SLC17A9	XM_011528978.3	c.-54A>G		5_prime_UTR_variant	Exon 2 of 12		XP_011527280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A9	ENST00000370351.9	c.307A>G	p.Ile103Val	missense_variant	Exon 3 of 13	1	NM_022082.4	ENSP00000359376.4
SLC17A9	ENST00000370349.7	c.289A>G	p.Ile97Val	missense_variant	Exon 4 of 14	1		ENSP00000359374.3
SLC17A9	ENST00000411611.1	c.367A>G	p.Ile123Val	missense_variant	Exon 3 of 3	2		ENSP00000388215.1
SLC17A9	ENST00000488738.5	n.427A>G		non_coding_transcript_exon_variant	Exon 3 of 11	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1457198 Hom.: 0 Cov.: 34 AF XY: 0.00000414 AC XY: 3 AN XY: 724986

African (AFR) AF: 0.00 AC: 0 AN: 33358

American (AMR) AF: 0.00 AC: 0 AN: 43698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25978

East Asian (EAS) AF: 0.00 AC: 0 AN: 39242

South Asian (SAS) AF: 0.00 AC: 0 AN: 85704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1110540

Other (OTH) AF: 0.00 AC: 0 AN: 60134

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.307A>G (p.I103V) alteration is located in exon 3 (coding exon 3) of the SLC17A9 gene. This alteration results from a A to G substitution at nucleotide position 307, causing the isoleucine (I) at amino acid position 103 to be replaced by a valine (V). 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	0.083
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.6
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	T;.;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.8	L;.;.
PhyloP100		0.84
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.73	N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.020	D;D;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.086	B;B;.
Vest4		0.15
MutPred		0.58		Loss of glycosylation at S102 (P = 0.1804);.;.;
MVP		0.061
MPC		0.38
ClinPred		0.17	T
GERP RS		-0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.055
gMVP		0.17
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs1033287330; hg19: chr20-61588842;