rs6012006

Positions:

• chr20-46676386-A-C
• chr20-46676386-A-T

Variant summary

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

The NM_001011554.3(SLC13A3):​c.-127-6247T>G variant causes a intron change. 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 0.72 (38452 hom., cov: 20)
• Consequence: SLC13A3 NM_001011554.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: No conservation score assigned

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC13A3	NM_001011554.3	c.-127-6247T>G		intron_variant			NP_001011554.1
SLC13A3	NM_001193340.2	c.-127-6247T>G		intron_variant			NP_001180269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC13A3	ENST00000372121.5	c.-31+8010T>G		intron_variant		5		ENSP00000361193

Frequencies

GnomAD3 genomes AF: 0.724 AC: 103707 AN: 143210 Hom.: 38407 Cov.: 20

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.724 AC: 103799 AN: 143294 Hom.: 38452 Cov.: 20 AF XY: 0.719 AC XY: 49808 AN XY: 69232

Gnomad4 AFR AF: 0.907

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.670

Alfa AF: 0.706 Hom.: 4445

Bravo AF: 0.724

Asia WGS AF: 0.578 AC: 2009 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.38

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6012006; hg19: chr20-45305025; COSMIC: COSV71977340;