20-62953231-C-A

Variant names:

• chr20-62953231-C-A
• rs578117224
• ENST00000370349.7:c.-1C>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The ENST00000370349.7(SLC17A9):​c.-1C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,550,402 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00077 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (2 hom.)
• Consequence: SLC17A9 ENST00000370349.7 5_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.676
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.754818).
• BP6: Variant 20-62953231-C-A is Benign according to our data. Variant chr20-62953231-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3034667.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 118 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A9	NM_022082.4	c.59+342C>A		intron_variant	Intron 1 of 12	ENST00000370351.9	NP_071365.4
SLC17A9	NM_001302643.2	c.-1C>A		5_prime_UTR_variant	Exon 2 of 14		NP_001289572.2
SLC17A9	XR_936601.4	n.181+342C>A		intron_variant	Intron 1 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A9	ENST00000370349.7	c.-1C>A		5_prime_UTR_variant	Exon 2 of 14	1		ENSP00000359374.3
SLC17A9	ENST00000370351.9	c.59+342C>A		intron_variant	Intron 1 of 12	1	NM_022082.4	ENSP00000359376.4
SLC17A9	ENST00000411611.1	c.78C>A	p.Cys26*	stop_gained	Exon 1 of 3	2		ENSP00000388215.1
SLC17A9	ENST00000488738.5	n.179+342C>A		intron_variant	Intron 1 of 10	2

Frequencies

GnomAD3 genomes AF: 0.000775 AC: 118 AN: 152164 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00100

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000839 AC: 123 AN: 146666 AF XY: 0.000948

Gnomad AFR exome AF: 0.000296

Gnomad AMR exome AF: 0.000244

Gnomad ASJ exome AF: 0.00263

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000655

Gnomad NFE exome AF: 0.00153

Gnomad OTH exome AF: 0.000705

GnomAD4 exome AF: 0.00111 AC: 1557 AN: 1398120 Hom.: 2 Cov.: 32 AF XY: 0.00114 AC XY: 785 AN XY: 689566

African (AFR) AF: 0.000158 AC: 5 AN: 31598

American (AMR) AF: 0.000168 AC: 6 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00282 AC: 71 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.000290 AC: 23 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48144

Middle Eastern (MID) AF: 0.000527 AC: 3 AN: 5696

European-Non Finnish (NFE) AF: 0.00128 AC: 1382 AN: 1078852

Other (OTH) AF: 0.00116 AC: 67 AN: 57984

GnomAD4 genome AF: 0.000775 AC: 118 AN: 152282 Hom.: 0 Cov.: 33 AF XY: 0.000792 AC XY: 59 AN XY: 74456

African (AFR) AF: 0.000337 AC: 14 AN: 41558

American (AMR) AF: 0.00144 AC: 22 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00100 AC: 68 AN: 68018

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00100 Hom.: 0

Bravo AF: 0.000982

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00130 AC: 5

ExAC AF: 0.000463 AC: 11

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SLC17A9-related disorder Benign:1

Jul 26, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.51
DANN	Benign	0.87
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.022	N
PhyloP100		-0.68
GERP RS		-4.6
PromoterAI		-0.0038	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs578117224; hg19: chr20-61584583;