20-46593296-A-C

Variant names:

• chr20-46593296-A-C
• rs126917
• NM_022829.6:c.795-767T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022829.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A3	NM_022829.6	MANE Select	c.795-767T>G		intron	N/A	NP_073740.2
	SLC13A3	NM_001011554.3		c.654-767T>G		intron	N/A	NP_001011554.1
	SLC13A3	NM_001193339.2		c.728-850T>G		intron	N/A	NP_001180268.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A3	ENST00000279027.9	TSL:1 MANE Select	c.795-767T>G		intron	N/A	ENSP00000279027.4
	SLC13A3	ENST00000495082.5	TSL:1	c.654-767T>G		intron	N/A	ENSP00000419621.1
	SLC13A3	ENST00000290317.9	TSL:5	c.654-767T>G		intron	N/A	ENSP00000290317.5

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

African (AFR) AF: 0.494 AC: 20478 AN: 41448

American (AMR) AF: 0.257 AC: 3929 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3472

East Asian (EAS) AF: 0.495 AC: 2557 AN: 5170

South Asian (SAS) AF: 0.125 AC: 604 AN: 4820

European-Finnish (FIN) AF: 0.187 AC: 1984 AN: 10582

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11127 AN: 67996

Other (OTH) AF: 0.230 AC: 485 AN: 2112

Alfa AF: 0.198 Hom.: 15528

Bravo AF: 0.294

Asia WGS AF: 0.335 AC: 1165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.0
DANN	Benign	0.89
PhyloP100		-0.51
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: rs126917; hg19: chr20-45221935;