20-46649530-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.111+1781T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,042 control chromosomes in the GnomAD database, including 40,417 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 0.72 (40417 hom., cov: 31)
• Consequence: SLC13A3 NM_022829.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69

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=-0.91).
• 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	UniProt
SLC13A3	NM_022829.6	c.111+1781T>C		intron_variant		ENST00000279027.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC13A3	ENST00000279027.9	c.111+1781T>C		intron_variant		1	NM_022829.6	P1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109165 AN: 151924 Hom.: 40368 Cov.: 31

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.719 AC: 109273 AN: 152042 Hom.: 40417 Cov.: 31 AF XY: 0.713 AC XY: 52950 AN XY: 74304

Gnomad4 AFR AF: 0.907

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.667

Gnomad4 OTH AF: 0.662

Alfa AF: 0.664 Hom.: 68485

Bravo AF: 0.722

Asia WGS AF: 0.588 AC: 2047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.032
Dann	Benign	0.27

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: rs1004571; hg19: chr20-45278169;