20-62952880-A-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022082.4(SLC17A9):c.50A>C(p.Gln17Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000011 in 911,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q17R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0000011 ( 0 hom. )

Consequence

SLC17A9
NM_022082.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.03

Publications

0 publications found

Variant links:

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)

SLC17A9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13563788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A9	NM_022082.4 link	c.50A>C	p.Gln17Pro	missense_variant	Exon 1 of 13	ENST00000370351.9	NP_071365.4	Q9BYT1-1
SLC17A9	XR_936601.4 link	n.172A>C		non_coding_transcript_exon_variant	Exon 1 of 10
SLC17A9	NM_001302643.2 link	c.-31A>C		5_prime_UTR_variant	Exon 1 of 14		NP_001289572.2	Q9BYT1-2H0UI90

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC17A9	ENST00000370351.9 link	c.50A>C	p.Gln17Pro	missense_variant	Exon 1 of 13	1	NM_022082.4	ENSP00000359376.4	Q9BYT1-1
SLC17A9	ENST00000370349.7 link	c.-31A>C		5_prime_UTR_variant	Exon 1 of 14	1		ENSP00000359374.3	Q9BYT1-2
SLC17A9	ENST00000488738.5 link	n.170A>C		non_coding_transcript_exon_variant	Exon 1 of 11	2
SLC17A9	ENST00000411611.1 link	c.-274A>C		upstream_gene_variant		2		ENSP00000388215.1	Q5W197

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000110

AC:

AN:

911934

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

446634

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20066

American (AMR)

AF:

0.00

AC:

AN:

22678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12422

East Asian (EAS)

AF:

0.00

AC:

AN:

11756

South Asian (SAS)

AF:

0.00

AC:

AN:

63344

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2186

European-Non Finnish (NFE)

AF:

0.00000136

AC:

AN:

734234

Other (OTH)

AF:

0.00

AC:

AN:

32876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 01, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.50A>C (p.Q17P) alteration is located in exon 1 (coding exon 1) of the SLC17A9 gene. This alteration results from a A to C substitution at nucleotide position 50, causing the glutamine (Q) at amino acid position 17 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.6

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.11

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.41

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

-1.0

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.5

REVEL

Benign

0.036

Sift

Benign

0.19

Sift4G

Benign

0.20

Polyphen

0.28

Vest4

0.14

MVP

0.076

MPC

0.53

ClinPred

0.082

GERP RS

-0.76

PromoterAI

-0.013

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.16

gMVP

0.29

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over