10-59654442-T-C

Position:

• chr10-59654442-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_194298.3(SLC16A9):​c.584A>G​(p.Asp195Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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)
• Consequence: SLC16A9 NM_194298.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.161

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034683615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC16A9	NM_194298.3	c.584A>G	p.Asp195Gly	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.584A>G	p.Asp195Gly	missense_variant	5/6	5	NM_194298.3	ENSP00000378757.3
SLC16A9	ENST00000395347.1	c.584A>G	p.Asp195Gly	missense_variant	5/6	2		ENSP00000378756.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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

Sep 22, 2023

The c.584A>G (p.D195G) alteration is located in exon 5 (coding exon 4) of the SLC16A9 gene. This alteration results from a A to G substitution at nucleotide position 584, causing the aspartic acid (D) at amino acid position 195 to be replaced by a glycine (G). 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	0.070
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.0
DANN	Benign	0.79
DEOGEN2	Benign	0.050	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.62	.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.035	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.39	N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.62	N;N
REVEL	Benign	0.15
Sift	Benign	0.44	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.11
MutPred		0.50		Gain of glycosylation at S194 (P = 0.0246);Gain of glycosylation at S194 (P = 0.0246);
MVP		0.15
MPC		0.16
ClinPred		0.025	T
GERP RS		-0.25
Varity_R		0.079
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-61414200;