20-62956941-T-G

Variant names:

• chr20-62956941-T-G
• rs1601086575
• NM_022082.4:c.236T>G

Variant summary

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

The NM_022082.4(SLC17A9):​c.236T>G​(p.Val79Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. V79A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SLC17A9 NM_022082.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.43
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A9	NM_022082.4	c.236T>G	p.Val79Gly	missense_variant	Exon 2 of 13	ENST00000370351.9	NP_071365.4
SLC17A9	NM_001302643.2	c.218T>G	p.Val73Gly	missense_variant	Exon 3 of 14		NP_001289572.2
SLC17A9	XR_936601.4	n.358T>G		non_coding_transcript_exon_variant	Exon 2 of 10
SLC17A9	XM_011528978.3	c.-104+5T>G		splice_region_variant, intron_variant	Intron 1 of 11		XP_011527280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A9	ENST00000370351.9	c.236T>G	p.Val79Gly	missense_variant	Exon 2 of 13	1	NM_022082.4	ENSP00000359376.4
SLC17A9	ENST00000370349.7	c.218T>G	p.Val73Gly	missense_variant	Exon 3 of 14	1		ENSP00000359374.3
SLC17A9	ENST00000411611.1	c.296T>G	p.Val99Gly	missense_variant	Exon 2 of 3	2		ENSP00000388215.1
SLC17A9	ENST00000488738.5	n.356T>G		non_coding_transcript_exon_variant	Exon 2 of 11	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 78

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D;.;.
Eigen	Benign	-0.011
Eigen_PC	Benign	0.047
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.79	T;T;D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.4	L;.;.
PhyloP100		4.4
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-4.9	D;D;D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		0.19	B;B;.
Vest4		0.49
MutPred		0.72		Loss of stability (P = 0.0042);.;.;
MVP		0.58
MPC		0.87
ClinPred		0.94	D
GERP RS		3.7
Varity_R		0.61
gMVP		0.38
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs1601086575; hg19: chr20-61588293;