rs188700676

Positions:

• chr20-46560194-C-A
• chr20-46560194-C-T

Variant summary

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

The NM_022829.6(SLC13A3):​c.1637G>T​(p.Arg546Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC13A3 NM_022829.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.98

Genes affected

SLC13A3 (HGNC:14430): (solute carrier family 13 member 3) Mammalian sodium-dicarboxylate cotransporters transport succinate and other Krebs cycle intermediates. They fall into 2 categories based on their substrate affinity: low affinity and high affinity. Both the low- and high-affinity transporters play an important role in the handling of citrate by the kidneys. The protein encoded by this gene represents the high-affinity form. Alternatively spliced transcript variants encoding different isoforms have been found for this gene, although the full-length nature of some of them have not been characterized yet. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC13A3	NM_022829.6	c.1637G>T	p.Arg546Leu	missense_variant	13/13	ENST00000279027.9	NP_073740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC13A3	ENST00000279027.9	c.1637G>T	p.Arg546Leu	missense_variant	13/13	1	NM_022829.6	ENSP00000279027.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	.;T;.;.;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D;D;D;D;.
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.67	D;D;D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.4	.;M;.;.;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-4.5	D;D;D;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Benign	0.070	T;T;T;T;T
Polyphen		0.97, 0.94	.;D;P;.;.
Vest4		0.59
MutPred		0.70		.;Loss of methylation at R546 (P = 0.0167);.;.;.;
MVP		0.58
MPC		1.0
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.38
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr20-45188833;