20-46575896-G-T

Variant names:

• chr20-46575896-G-T
• rs393990
• NM_022829.6:c.1220-211C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022829.6(SLC13A3):​c.1220-211C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,096 control chromosomes in the GnomAD database, including 49,029 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 0.80 (49029 hom., cov: 31)
• Consequence: SLC13A3 NM_022829.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840
• Publications: 6 publications found

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]

SLC13A3 Gene-Disease associations (from GenCC):

• leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC13A3	NM_022829.6	c.1220-211C>A		intron_variant	Intron 9 of 12	ENST00000279027.9	NP_073740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC13A3	ENST00000279027.9	c.1220-211C>A		intron_variant	Intron 9 of 12	1	NM_022829.6	ENSP00000279027.4

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121708 AN: 151976 Hom.: 49006 Cov.: 31

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.801 AC: 121783 AN: 152096 Hom.: 49029 Cov.: 31 AF XY: 0.801 AC XY: 59551 AN XY: 74352

African (AFR) AF: 0.710 AC: 29425 AN: 41454

American (AMR) AF: 0.829 AC: 12664 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2865 AN: 3470

East Asian (EAS) AF: 0.869 AC: 4487 AN: 5162

South Asian (SAS) AF: 0.865 AC: 4175 AN: 4824

European-Finnish (FIN) AF: 0.829 AC: 8774 AN: 10588

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.835 AC: 56748 AN: 67998

Other (OTH) AF: 0.807 AC: 1704 AN: 2112

Alfa AF: 0.821 Hom.: 95954

Bravo AF: 0.796

Asia WGS AF: 0.880 AC: 3057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.39
PhyloP100		0.084
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs393990; hg19: chr20-45204535;