chr20-46560027-G-A

Position:

• chr20-46560027-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022829.6(SLC13A3):​c.1804C>T​(p.Leu602Phe) 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. 15/21 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: SLC13A3 NM_022829.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.82

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.114273876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC13A3	NM_022829.6	c.1804C>T	p.Leu602Phe	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.1804C>T	p.Leu602Phe	missense_variant	13/13	1	NM_022829.6	ENSP00000279027	P1

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 provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 26, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The phenylalanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with SLC13A3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 602 of the SLC13A3 protein (p.Leu602Phe). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.13	.;T;.;.;.
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.65
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.80	T;T;T;T;.
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	.;L;.;.;.
MutationTaster	Benign	0.99	N;N;N;N;N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.76	N;N;N;N;N
REVEL	Benign	0.059
Sift	Uncertain	0.0070	D;D;D;D;D
Sift4G	Uncertain	0.018	D;D;D;D;D
Polyphen		0.89, 0.010	.;P;B;.;.
Vest4		0.11
MutPred		0.29		.;Gain of solvent accessibility (P = 0.0917);.;.;.;
MVP		0.24
MPC		0.86
ClinPred		0.33	T
GERP RS		0.90
Varity_R		0.033
gMVP		0.53

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: chr20-45188666;