20-62952870-G-C

Variant names:

• chr20-62952870-G-C
• rs1426740759
• NM_022082.4:c.40G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022082.4(SLC17A9):​c.40G>C​(p.Gly14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000219 in 1,367,574 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: 30)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: SLC17A9 NM_022082.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.297
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040297568).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022082.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC17A9	NM_022082.4	MANE Select	c.40G>C	p.Gly14Arg	missense	Exon 1 of 13	NP_071365.4
	SLC17A9	NM_001302643.2		c.-41G>C		5_prime_UTR	Exon 1 of 14	NP_001289572.2	Q9BYT1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC17A9	ENST00000370351.9	TSL:1 MANE Select	c.40G>C	p.Gly14Arg	missense	Exon 1 of 13	ENSP00000359376.4	Q9BYT1-1
	SLC17A9	ENST00000370349.7	TSL:1	c.-41G>C		5_prime_UTR	Exon 1 of 14	ENSP00000359374.3	Q9BYT1-2
	SLC17A9	ENST00000878413.1		c.40G>C	p.Gly14Arg	missense	Exon 1 of 14	ENSP00000548472.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000219 AC: 3 AN: 1367574 Hom.: 0 Cov.: 34 AF XY: 0.00000297 AC XY: 2 AN XY: 673944

African (AFR) AF: 0.00 AC: 0 AN: 31030

American (AMR) AF: 0.00 AC: 0 AN: 33156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24048

East Asian (EAS) AF: 0.0000563 AC: 2 AN: 35500

South Asian (SAS) AF: 0.00 AC: 0 AN: 77030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35670

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3988

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1070252

Other (OTH) AF: 0.0000176 AC: 1 AN: 56900

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	11
DANN	Benign	0.54
DEOGEN2	Benign	0.033	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.30
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.38	N
REVEL	Benign	0.020
Sift	Benign	0.46	T
Sift4G	Benign	0.49	T
Polyphen		0.0030	B
Vest4		0.055
MutPred		0.30		Gain of solvent accessibility (P = 0.0306)
MVP		0.061
MPC		0.52
ClinPred		0.026	T
GERP RS		0.99
PromoterAI		0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.013
gMVP		0.069
Mutation Taster		=97/3	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: rs1426740759; hg19: chr20-61584222;