20-62952855-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_022082.4(SLC17A9):c.25C>T(p.Arg9Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000766 in 1,474,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R9H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

SLC17A9
NM_022082.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 0.208

Publications

5 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:

ENSG00000302769 (HGNC:):

ENSG00000302769 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.039606154).

BS2

High AC in GnomAd4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A9	NM_022082.4 link	c.25C>T	p.Arg9Cys	missense_variant	Exon 1 of 13	ENST00000370351.9	NP_071365.4	Q9BYT1-1
SLC17A9	NM_001302643.2 link	c.-56C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 14		NP_001289572.2	Q9BYT1-2H0UI90
SLC17A9	XR_936601.4 link	n.147C>T		non_coding_transcript_exon_variant	Exon 1 of 10
SLC17A9	NM_001302643.2 link	c.-56C>T		5_prime_UTR_variant	Exon 1 of 14		NP_001289572.2	Q9BYT1-2H0UI90

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A9	ENST00000370351.9 link	c.25C>T	p.Arg9Cys	missense_variant	Exon 1 of 13	1	NM_022082.4	ENSP00000359376.4		Q9BYT1-1

Frequencies

GnomAD3 genomes

AF:

0.000140

AC:

AN:

142856

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00407

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000303

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000231

AC:

AN:

130148

AF XY:

0.000170

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000205

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000698

AC:

AN:

1331734

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

655646

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30080

American (AMR)

AF:

0.0000601

AC:

AN:

33290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23000

East Asian (EAS)

AF:

0.00194

AC:

AN:

32476

South Asian (SAS)

AF:

0.0000257

AC:

AN:

77900

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32994

Middle Eastern (MID)

AF:

0.000263

AC:

AN:

3804

European-Non Finnish (NFE)

AF:

0.0000211

AC:

AN:

1044136

Other (OTH)

AF:

0.0000555

AC:

AN:

54054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000140

AC:

AN:

142948

Hom.:

Cov.:

AF XY:

0.000144

AC XY:

AN XY:

69254

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38694

American (AMR)

AF:

0.00

AC:

AN:

14212

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3392

East Asian (EAS)

AF:

0.00407

AC:

AN:

4418

South Asian (SAS)

AF:

0.00

AC:

AN:

4164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8892

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000303

AC:

AN:

65998

Other (OTH)

AF:

0.00

AC:

AN:

2008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000196

Asia WGS

AF:

0.000579

AC:

AN:

3470

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Porokeratosis 8, disseminated superficial actinic type

Pathogenic:1

Oct 01, 2014

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not specified

Uncertain:1

May 04, 2022

Mendelics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.052

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.53

M_CAP

Pathogenic

0.84

MetaRNN

Benign

0.040

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.9

PhyloP100

0.21

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.5

REVEL

Pathogenic

0.66

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.018

Polyphen

0.48

Vest4

0.074

MutPred

0.32

Loss of solvent accessibility (P = 0.0036);

MVP

0.23

MPC

0.59

ClinPred

0.069

GERP RS

3.0

PromoterAI

0.012

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.10

gMVP

0.30

Mutation Taster

=90/10

disease causing (ClinVar)

(source)

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

Publications

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20-62952855-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over