10-59652882-C-T

Variant names:

• chr10-59652882-C-T
• NM_194298.3:c.1420G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_194298.3(SLC16A9):​c.1420G>A​(p.Gly474Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC16A9 NM_194298.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.20
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.888

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A9	NM_194298.3	c.1420G>A	p.Gly474Arg	missense_variant	Exon 6 of 6	ENST00000395348.8	NP_919274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC16A9	ENST00000395348.8	c.1420G>A	p.Gly474Arg	missense_variant	Exon 6 of 6	5	NM_194298.3	ENSP00000378757.3
SLC16A9	ENST00000395347.1	c.1420G>A	p.Gly474Arg	missense_variant	Exon 6 of 6	2		ENSP00000378756.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1420G>A (p.G474R) 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 1420, causing the glycine (G) at amino acid position 474 to be replaced by an arginine (R). 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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.24	T;T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	.;D
M_CAP	Uncertain	0.088	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Uncertain	0.56	D
MutationAssessor	Uncertain	2.7	M;M
PhyloP100		7.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.8	D;D
REVEL	Pathogenic	0.86
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;D
Vest4		0.87
MutPred		0.73		Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);
MVP		0.93
MPC		0.63
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.66
gMVP		0.96
Mutation Taster		=46/54	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr10-61412640;