20-62952868-C-T

Variant names:

• chr20-62952868-C-T
• rs2065502161
• NM_022082.4:c.38C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022082.4(SLC17A9):​c.38C>T​(p.Ala13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000175 in 1,139,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. A13D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: SLC17A9 NM_022082.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.495
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20077786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A9	NM_022082.4	c.38C>T	p.Ala13Val	missense_variant	Exon 1 of 13	ENST00000370351.9	NP_071365.4
SLC17A9	XR_936601.4	n.160C>T		non_coding_transcript_exon_variant	Exon 1 of 10
SLC17A9	NM_001302643.2	c.-43C>T		5_prime_UTR_variant	Exon 1 of 14		NP_001289572.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A9	ENST00000370351.9	c.38C>T	p.Ala13Val	missense_variant	Exon 1 of 13	1	NM_022082.4	ENSP00000359376.4
SLC17A9	ENST00000370349.7	c.-43C>T		5_prime_UTR_variant	Exon 1 of 14	1		ENSP00000359374.3
SLC17A9	ENST00000488738.5	n.158C>T		non_coding_transcript_exon_variant	Exon 1 of 11	2
SLC17A9	ENST00000411611.1	c.-286C>T		upstream_gene_variant		2		ENSP00000388215.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000175 AC: 2 AN: 1139948 Hom.: 0 Cov.: 33 AF XY: 0.00000179 AC XY: 1 AN XY: 558384

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24440

American (AMR) AF: 0.00 AC: 0 AN: 26354

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15526

East Asian (EAS) AF: 0.00 AC: 0 AN: 14786

South Asian (SAS) AF: 0.00 AC: 0 AN: 74562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16878

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2784

European-Non Finnish (NFE) AF: 0.00000217 AC: 2 AN: 922828

Other (OTH) AF: 0.00 AC: 0 AN: 41790

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.006664), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.54	T
M_CAP	Pathogenic	0.64	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	M
PhyloP100		0.49
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.17
Sift	Benign	0.17	T
Sift4G	Benign	0.24	T
Polyphen		0.70	P
Vest4		0.11
MutPred		0.25		Loss of disorder (P = 0.0727);
MVP		0.20
MPC		0.48
ClinPred		0.18	T
GERP RS		3.0
PromoterAI		0.00070	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.035
gMVP		0.24
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2065502161; hg19: chr20-61584220;