rs6066043

Positions:

• chr20-46659814-G-A
• chr20-46659814-G-T

Variant summary

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

The ENST00000417157.2(SLC13A3):​c.-31+10229C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 149,636 control chromosomes in the GnomAD database, including 1,995 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 0.13 (1995 hom., cov: 31)
• Consequence: SLC13A3 ENST00000417157.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC13A3	NM_001011554.3	c.-31+10229C>T		intron_variant			NP_001011554.1
SLC13A3	NM_001193340.2	c.-31+10229C>T		intron_variant			NP_001180269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC13A3	ENST00000417157.2	c.-31+10229C>T		intron_variant		1		ENSP00000397955
SLC13A3	ENST00000290317.9	c.-31+10229C>T		intron_variant		5		ENSP00000290317
SLC13A3	ENST00000372121.5	c.-31+24582C>T		intron_variant		5		ENSP00000361193

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19395 AN: 149522 Hom.: 1999 Cov.: 31

Gnomad AFR AF: 0.0297

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.0763

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.130 AC: 19392 AN: 149636 Hom.: 1995 Cov.: 31 AF XY: 0.138 AC XY: 10049 AN XY: 72834

Gnomad4 AFR AF: 0.0296

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.0763

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.152

Alfa AF: 0.136 Hom.: 2027

Bravo AF: 0.127

Asia WGS AF: 0.360 AC: 1249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.2
DANN	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6066043; hg19: chr20-45288453;