10-59652860-G-A

Position:

• chr10-59652860-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_194298.3(SLC16A9):​c.1442C>T​(p.Ala481Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SLC16A9 NM_194298.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.78

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12904683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC16A9	NM_194298.3	c.1442C>T	p.Ala481Val	missense_variant	6/6	ENST00000395348.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC16A9	ENST00000395348.8	c.1442C>T	p.Ala481Val	missense_variant	6/6	5	NM_194298.3	P1
SLC16A9	ENST00000395347.1	c.1442C>T	p.Ala481Val	missense_variant	6/6	2		P1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74332

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000843 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2023

The c.1442C>T (p.A481V) alteration is located in exon 6 (coding exon 5) of the SLC16A9 gene. This alteration results from a C to T substitution at nucleotide position 1442, causing the alanine (A) at amino acid position 481 to be replaced by a valine (V). 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	0.10
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Benign	0.91
DEOGEN2	Benign	0.0073	T;T
Eigen	Benign	-0.23
Eigen_PC	Benign	0.030
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.69	N;N
MutationTaster	Benign	0.96	D;D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.19	N;N
REVEL	Benign	0.20
Sift	Benign	0.45	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0040	B;B
Vest4		0.18
MutPred		0.39		Loss of loop (P = 0.0022);Loss of loop (P = 0.0022);
MVP		0.18
MPC		0.13
ClinPred		0.67	D
GERP RS		4.7
Varity_R		0.049
gMVP		0.18

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

LitVar

Other links and lift over

dbSNP: rs1332229564; hg19: chr10-61412618;