rs126917

Positions:

• chr20-46593296-A-C
• chr20-46593296-A-G

Variant summary

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

The NM_022829.6(SLC13A3):​c.795-767T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,094 control chromosomes in the GnomAD database, including 7,491 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (7491 hom., cov: 32)
• Consequence: SLC13A3 NM_022829.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC13A3	NM_022829.6	c.795-767T>G		intron_variant		ENST00000279027.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC13A3	ENST00000279027.9	c.795-767T>G		intron_variant		1	NM_022829.6	P1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41680 AN: 151976 Hom.: 7461 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.223

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.275 AC: 41765 AN: 152094 Hom.: 7491 Cov.: 32 AF XY: 0.275 AC XY: 20431 AN XY: 74364

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.230

Alfa AF: 0.177 Hom.: 5321

Bravo AF: 0.294

Asia WGS AF: 0.335 AC: 1165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.0
DANN	Benign	0.89

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: rs126917; hg19: chr20-45221935;