20-62952855-C-T

Position:

• chr20-62952855-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001302643.2(SLC17A9):​c.-56C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000766 in 1,474,682 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 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000070 (0 hom.)
• Consequence: SLC17A9 NM_001302643.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1
• 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]

SLC17A9 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.039606154).
• BS2: High AC in GnomAd4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC17A9	NM_022082.4	c.25C>T	p.Arg9Cys	missense_variant	1/13	ENST00000370351.9	NP_071365.4
SLC17A9	NM_001302643.2	c.-56C>T		5_prime_UTR_premature_start_codon_gain_variant	1/14		NP_001289572.2
SLC17A9	NM_001302643.2	c.-56C>T		5_prime_UTR_variant	1/14		NP_001289572.2
SLC17A9	XR_936601.4	n.147C>T		non_coding_transcript_exon_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC17A9	ENST00000370349	c.-56C>T		5_prime_UTR_premature_start_codon_gain_variant	1/14	1		ENSP00000359374.3
SLC17A9	ENST00000370351.9	c.25C>T	p.Arg9Cys	missense_variant	1/13	1	NM_022082.4	ENSP00000359376.4
SLC17A9	ENST00000370349	c.-56C>T		5_prime_UTR_variant	1/14	1		ENSP00000359374.3
SLC17A9	ENST00000488738.5	n.145C>T		non_coding_transcript_exon_variant	1/11	2

Frequencies

GnomAD3 genomes AF: 0.000140 AC: 20 AN: 142856 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00407

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000303

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000231 AC: 30 AN: 130148 Hom.: 0 AF XY: 0.000170 AC XY: 12 AN XY: 70526

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00261

Gnomad SAS exome AF: 0.0000922

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000205

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000698 AC: 93 AN: 1331734 Hom.: 0 Cov.: 33 AF XY: 0.0000564 AC XY: 37 AN XY: 655646

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000601

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00194

Gnomad4 SAS exome AF: 0.0000257

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000211

Gnomad4 OTH exome AF: 0.0000555

GnomAD4 genome AF: 0.000140 AC: 20 AN: 142948 Hom.: 0 Cov.: 32 AF XY: 0.000144 AC XY: 10 AN XY: 69254

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00407

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000303

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000196

Asia WGS AF: 0.000579 AC: 2 AN: 3470

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1 Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Porokeratosis 8, disseminated superficial actinic type Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 01, 2014

- -

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.53	T
M_CAP	Pathogenic	0.84	D
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.9	M
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.5	N
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.018	D
Polyphen		0.48	P
Vest4		0.074
MutPred		0.32		Loss of solvent accessibility (P = 0.0036);
MVP		0.23
MPC		0.59
ClinPred		0.069	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.30

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;