20-46630992-T-C

Variant names:

• chr20-46630992-T-C
• rs2425885
• NM_022829.6:c.112-17267A>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.112-17267A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,254 control chromosomes in the GnomAD database, including 871 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 0.10 (871 hom., cov: 32)
• Consequence: SLC13A3 NM_022829.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 1 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 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.112-17267A>G		intron	N/A	NP_073740.2
	SLC13A3	NM_001011554.3		c.-30-17267A>G		intron	N/A	NP_001011554.1
	SLC13A3	NM_001193339.2		c.112-17267A>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.112-17267A>G		intron	N/A	ENSP00000279027.4
	SLC13A3	ENST00000417157.2	TSL:1	c.-30-17267A>G		intron	N/A	ENSP00000397955.2
	SLC13A3	ENST00000290317.9	TSL:5	c.-30-17267A>G		intron	N/A	ENSP00000290317.5

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15649 AN: 152136 Hom.: 868 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0786

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.00577

Gnomad SAS AF: 0.0702

Gnomad FIN AF: 0.0754

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0984

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.103 AC: 15684 AN: 152254 Hom.: 871 Cov.: 32 AF XY: 0.100 AC XY: 7450 AN XY: 74438

African (AFR) AF: 0.147 AC: 6089 AN: 41534

American (AMR) AF: 0.0784 AC: 1200 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0720 AC: 250 AN: 3470

East Asian (EAS) AF: 0.00579 AC: 30 AN: 5184

South Asian (SAS) AF: 0.0702 AC: 339 AN: 4826

European-Finnish (FIN) AF: 0.0754 AC: 799 AN: 10602

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0984 AC: 6691 AN: 68018

Other (OTH) AF: 0.112 AC: 236 AN: 2112

Alfa AF: 0.100 Hom.: 299

Bravo AF: 0.105

Asia WGS AF: 0.0630 AC: 217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.24
DANN	Benign	0.90
PhyloP100		-1.0
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: rs2425885; hg19: chr20-45259631;