10-59654226-G-C

Variant names:

• chr10-59654226-G-C
• rs770783816
• NM_194298.3:c.800C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_194298.3(SLC16A9):​c.800C>G​(p.Thr267Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,874 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T267M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC16A9 NM_194298.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.60
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2625159).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A9	NM_194298.3	c.800C>G	p.Thr267Arg	missense_variant	Exon 5 of 6	ENST00000395348.8	NP_919274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC16A9	ENST00000395348.8	c.800C>G	p.Thr267Arg	missense_variant	Exon 5 of 6	5	NM_194298.3	ENSP00000378757.3
SLC16A9	ENST00000395347.1	c.800C>G	p.Thr267Arg	missense_variant	Exon 5 of 6	2		ENSP00000378756.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251372 AF XY: 0.00000736

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: 0.00000205 AC: 3 AN: 1461874 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.065	T;T
Eigen	Benign	0.11
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.82	.;T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L;L
PhyloP100		3.6
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.50	N;N
REVEL	Benign	0.10
Sift	Benign	0.56	T;T
Sift4G	Benign	0.23	T;T
Polyphen		0.96	D;D
Vest4		0.45
MutPred		0.44		Loss of phosphorylation at T267 (P = 0.0107);Loss of phosphorylation at T267 (P = 0.0107);
MVP		0.28
MPC		0.43
ClinPred		0.60	D
GERP RS		4.1
Varity_R		0.090
gMVP		0.59
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

dbSNP: rs770783816; hg19: chr10-61413984;