chr20-62957513-C-T

Variant names:

• chr20-62957513-C-T
• rs76379118
• NM_022082.4:c.330C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_022082.4(SLC17A9):​c.330C>T​(p.Leu110Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 1,610,046 control chromosomes in the GnomAD database, including 3,380 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.050 (268 hom., cov: 33)
  • Exomes 𝑓: 0.062 (3112 hom.)
• Consequence: SLC17A9 NM_022082.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.495
• Publications: 8 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 20-62957513-C-T is Benign according to our data. Variant chr20-62957513-C-T is described in ClinVar as Benign. ClinVar VariationId is 3056817.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.495 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.069 is higher than 0.05.

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.330C>T	p.Leu110Leu	synonymous	Exon 3 of 13	NP_071365.4
	SLC17A9	NM_001302643.2		c.312C>T	p.Leu104Leu	synonymous	Exon 4 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.330C>T	p.Leu110Leu	synonymous	Exon 3 of 13	ENSP00000359376.4	Q9BYT1-1
	SLC17A9	ENST00000370349.7	TSL:1	c.312C>T	p.Leu104Leu	synonymous	Exon 4 of 14	ENSP00000359374.3	Q9BYT1-2
	SLC17A9	ENST00000878413.1		c.330C>T	p.Leu110Leu	synonymous	Exon 3 of 14	ENSP00000548472.1

Frequencies

GnomAD3 genomes AF: 0.0500 AC: 7605 AN: 152148 Hom.: 268 Cov.: 33

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0391

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0310

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0707

Gnomad OTH AF: 0.0458

GnomAD2 exomes AF: 0.0519 AC: 12707 AN: 244648 AF XY: 0.0529

Gnomad AFR exome AF: 0.0109

Gnomad AMR exome AF: 0.0230

Gnomad ASJ exome AF: 0.0470

Gnomad EAS exome AF: 0.000571

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.0715

Gnomad OTH exome AF: 0.0556

GnomAD4 exome AF: 0.0624 AC: 90936 AN: 1457780 Hom.: 3112 Cov.: 34 AF XY: 0.0612 AC XY: 44415 AN XY: 725264

African (AFR) AF: 0.0101 AC: 337 AN: 33396

American (AMR) AF: 0.0248 AC: 1089 AN: 43846

Ashkenazi Jewish (ASJ) AF: 0.0458 AC: 1193 AN: 26030

East Asian (EAS) AF: 0.000483 AC: 19 AN: 39340

South Asian (SAS) AF: 0.0313 AC: 2682 AN: 85808

European-Finnish (FIN) AF: 0.0975 AC: 5138 AN: 52692

Middle Eastern (MID) AF: 0.0242 AC: 139 AN: 5744

European-Non Finnish (NFE) AF: 0.0694 AC: 77057 AN: 1110770

Other (OTH) AF: 0.0546 AC: 3282 AN: 60154

GnomAD4 genome AF: 0.0499 AC: 7605 AN: 152266 Hom.: 268 Cov.: 33 AF XY: 0.0508 AC XY: 3782 AN XY: 74440

African (AFR) AF: 0.0129 AC: 535 AN: 41560

American (AMR) AF: 0.0391 AC: 598 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0438 AC: 152 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0317 AC: 153 AN: 4828

European-Finnish (FIN) AF: 0.110 AC: 1162 AN: 10600

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0707 AC: 4806 AN: 67996

Other (OTH) AF: 0.0454 AC: 96 AN: 2116

Alfa AF: 0.0592 Hom.: 175

Bravo AF: 0.0428

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SLC17A9-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.28
DANN	Benign	0.42
PhyloP100		-0.49
Mutation Taster		=99/1	polymorphism (auto)

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: rs76379118; hg19: chr20-61588865;