rs548728088

Positions:

• chr20-62952855-C-A
• chr20-62952855-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022082.4(SLC17A9):​c.25C>A​(p.Arg9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC17A9 NM_022082.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15380833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC17A9	NM_022082.4	c.25C>A	p.Arg9Ser	missense_variant	1/13	ENST00000370351.9	NP_071365.4
SLC17A9	NM_001302643.2	c.-56C>A		5_prime_UTR_variant	1/14		NP_001289572.2
SLC17A9	XR_936601.4	n.147C>A		non_coding_transcript_exon_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC17A9	ENST00000370351.9	c.25C>A	p.Arg9Ser	missense_variant	1/13	1	NM_022082.4	ENSP00000359376	P1
SLC17A9	ENST00000370349.7	c.-56C>A		5_prime_UTR_variant	1/14	1		ENSP00000359374
SLC17A9	ENST00000488738.5	n.145C>A		non_coding_transcript_exon_variant	1/11	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1331732 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 655646

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	5.7
DANN	Benign	0.95
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.42	T
M_CAP	Pathogenic	0.72	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	0.99	D;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.19
Sift	Benign	0.058	T
Sift4G	Benign	0.10	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.29		Gain of glycosylation at R9 (P = 0.0073);
MVP		0.18
MPC		0.50
ClinPred		0.22	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.077
gMVP		0.29

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: rs548728088; hg19: chr20-61584207;