rs2242206

Positions:

• chr10-59654253-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194298.3(SLC16A9):​c.773C>A​(p.Thr258Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,613,936 control chromosomes in the GnomAD database, including 76,315 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.26 (6446 hom., cov: 32)
  • Exomes 𝑓: 0.29 (69869 hom.)
• Consequence: SLC16A9 NM_194298.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.403912E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC16A9	NM_194298.3	c.773C>A	p.Thr258Lys	missense_variant	5/6	ENST00000395348.8	NP_919274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC16A9	ENST00000395348.8	c.773C>A	p.Thr258Lys	missense_variant	5/6	5	NM_194298.3	ENSP00000378757	P1
SLC16A9	ENST00000395347.1	c.773C>A	p.Thr258Lys	missense_variant	5/6	2		ENSP00000378756	P1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39287 AN: 151954 Hom.: 6432 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.246

GnomAD3 exomes AF: 0.344 AC: 86388 AN: 251450 Hom.: 17517 AF XY: 0.344 AC XY: 46799 AN XY: 135898

Gnomad AFR exome AF: 0.0975

Gnomad AMR exome AF: 0.462

Gnomad ASJ exome AF: 0.159

Gnomad EAS exome AF: 0.581

Gnomad SAS exome AF: 0.464

Gnomad FIN exome AF: 0.464

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.317

GnomAD4 exome AF: 0.295 AC: 431000 AN: 1461864 Hom.: 69869 Cov.: 50 AF XY: 0.299 AC XY: 217166 AN XY: 727230

Gnomad4 AFR exome AF: 0.0976

Gnomad4 AMR exome AF: 0.450

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.573

Gnomad4 SAS exome AF: 0.461

Gnomad4 FIN exome AF: 0.457

Gnomad4 NFE exome AF: 0.268

Gnomad4 OTH exome AF: 0.286

GnomAD4 genome AF: 0.259 AC: 39329 AN: 152072 Hom.: 6446 Cov.: 32 AF XY: 0.273 AC XY: 20265 AN XY: 74324

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.251

Alfa AF: 0.262 Hom.: 13873

Bravo AF: 0.241

TwinsUK AF: 0.263 AC: 974

ALSPAC AF: 0.262 AC: 1010

ESP6500AA AF: 0.106 AC: 468

ESP6500EA AF: 0.260 AC: 2235

ExAC AF: 0.335 AC: 40649

Asia WGS AF: 0.492 AC: 1709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.4
DANN	Benign	0.21
DEOGEN2	Benign	0.070	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.38	.;T
MetaRNN	Benign	0.000064	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.062
Sift	Benign	0.40	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.12	B;B
Vest4		0.12
MPC		0.17
ClinPred		0.0062	T
GERP RS		2.0
Varity_R		0.065
gMVP		0.37

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: rs2242206; hg19: chr10-61414011; COSMIC: COSV68100888; COSMIC: COSV68100888;