Genetic Variant SLC16A9:p.Val509Ile (chr10-59652777-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_194298.3(SLC16A9):c.1525G>A(p.Val509Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,456,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC16A9
NM_194298.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.15

Publications

0 publications found

Variant links:

Genes affected

SLC16A9 (HGNC:23520): (solute carrier family 16 member 9) Predicted to enable monocarboxylic acid transmembrane transporter activity. Involved in urate metabolic process. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC16A9 links:

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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=0.12307665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A9	NM_194298.3 link	c.1525G>A	p.Val509Ile	missense_variant	Exon 6 of 6	ENST00000395348.8	NP_919274.1	Q7RTY1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC16A9	ENST00000395348.8 link	c.1525G>A	p.Val509Ile	missense_variant	Exon 6 of 6	5	NM_194298.3	ENSP00000378757.3		Q7RTY1
SLC16A9	ENST00000395347.1 link	c.1525G>A	p.Val509Ile	missense_variant	Exon 6 of 6	2		ENSP00000378756.1		Q7RTY1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1456114

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33042

American (AMR)

AF:

0.00

AC:

AN:

43468

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25908

East Asian (EAS)

AF:

0.00

AC:

AN:

39550

South Asian (SAS)

AF:

0.00

AC:

AN:

84862

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1110064

Other (OTH)

AF:

0.0000166

AC:

AN:

60152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 09, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1525G>A (p.V509I) alteration is located in exon 6 (coding exon 5) of the SLC16A9 gene. This alteration results from a G to A substitution at nucleotide position 1525, causing the valine (V) at amino acid position 509 to be replaced by an isoleucine (I). 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

0.080

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0072

T;T

Eigen

Benign

0.020

Eigen_PC

Benign

0.22

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.55

.;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.69

N;N

PhyloP100

4.1

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.34

N;N

REVEL

Benign

0.083

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.19

B;B

Vest4

0.28

MutPred

0.25

Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);

MVP

0.043

MPC

0.42

ClinPred

0.60

GERP RS

5.6

Varity_R

0.14

gMVP

0.21

Mutation Taster

=88/12

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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10-59652777-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over