Genetic Variant NM_022082.4:c.40G>A (chr20-62952870-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_022082.4(SLC17A9):c.40G>A(p.Gly14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000592 in 1,519,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

SLC17A9
NM_022082.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.297

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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.039674312).

BS2

High AC in GnomAdExome4 at 6 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.40G>A	p.Gly14Arg	missense	Exon 1 of 13	NP_071365.4
	SLC17A9	NM_001302643.2		c.-41G>A		5_prime_UTR	Exon 1 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.40G>A	p.Gly14Arg	missense	Exon 1 of 13	ENSP00000359376.4	Q9BYT1-1
SLC17A9	ENST00000370349.7	TSL:1	c.-41G>A		5_prime_UTR	Exon 1 of 14	ENSP00000359374.3	Q9BYT1-2
SLC17A9	ENST00000878413.1		c.40G>A	p.Gly14Arg	missense	Exon 1 of 14	ENSP00000548472.1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151572

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000481

GnomAD2 exomes

AF:

0.00

AC:

AN:

117322

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

0.00000439

AC:

AN:

1367572

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

673944

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31030

American (AMR)

AF:

0.00

AC:

AN:

33156

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24048

East Asian (EAS)

AF:

0.0000563

AC:

AN:

35500

South Asian (SAS)

AF:

0.00

AC:

AN:

77030

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35670

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3988

European-Non Finnish (NFE)

AF:

0.00000280

AC:

AN:

1070250

Other (OTH)

AF:

0.0000176

AC:

AN:

56900

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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:

0.0000198

AC:

AN:

151572

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

73990

show subpopulations

African (AFR)

AF:

0.0000485

AC:

AN:

41222

American (AMR)

AF:

0.00

AC:

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67804

Other (OTH)

AF:

0.000481

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.033

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.43

M_CAP

Benign

0.078

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.30

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.38

REVEL

Benign

0.026

Sift

Benign

0.46

Sift4G

Benign

0.49

Polyphen

0.0070

Vest4

0.055

MutPred

0.30

Gain of solvent accessibility (P = 0.0306)

MVP

0.061

MPC

0.52

ClinPred

0.036

GERP RS

0.99

PromoterAI

-0.037

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.013

gMVP

0.069

Mutation Taster

=97/3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over