Genetic Variant SLC17A9:p.Ile64Phe (chr20-62956895-A-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_022082.4(SLC17A9):c.190A>T(p.Ile64Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,613,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

SLC17A9
NM_022082.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.451

Publications

2 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: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009948403).

BP6

Variant 20-62956895-A-T is Benign according to our data. Variant chr20-62956895-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3045682.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 180 AD gene.

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.190A>T	p.Ile64Phe	missense	Exon 2 of 13	NP_071365.4
	SLC17A9	NM_001302643.2		c.172A>T	p.Ile58Phe	missense	Exon 3 of 14	NP_001289572.2	Q9BYT1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC17A9	ENST00000370351.9	TSL:1 MANE Select	c.190A>T	p.Ile64Phe	missense	Exon 2 of 13	ENSP00000359376.4	Q9BYT1-1
SLC17A9	ENST00000370349.7	TSL:1	c.172A>T	p.Ile58Phe	missense	Exon 3 of 14	ENSP00000359374.3	Q9BYT1-2
SLC17A9	ENST00000878413.1		c.190A>T	p.Ile64Phe	missense	Exon 2 of 14	ENSP00000548472.1

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

179

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00417

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000428

AC:

106

AN:

247834

AF XY:

0.000312

show subpopulations

Gnomad AFR exome

AF:

0.00596

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000104

AC:

152

AN:

1461318

Hom.:

Cov.:

AF XY:

0.0000825

AC XY:

AN XY:

726978

show subpopulations

African (AFR)

AF:

0.00394

AC:

132

AN:

33480

American (AMR)

AF:

0.000268

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52876

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112000

Other (OTH)

AF:

0.000132

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00118

AC:

180

AN:

152342

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00418

AC:

174

AN:

41584

American (AMR)

AF:

0.000392

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000789

Hom.:

Bravo

AF:

0.00145

ESP6500AA

AF:

0.00424

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000537

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

SLC17A9-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.60

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.17

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.82

M_CAP

Benign

0.037

MetaRNN

Benign

0.0099

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

-0.45

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.8

REVEL

Benign

0.12

Sift

Uncertain

0.025

Sift4G

Benign

0.069

Polyphen

0.0070

Vest4

0.26

MVP

0.030

MPC

0.69

ClinPred

0.013

GERP RS

-4.1

Varity_R

0.18

gMVP

0.43

Mutation Taster

=83/17

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over