chr20-46659814-G-A

Variant names:

• chr20-46659814-G-A
• rs6066043
• ENST00000417157.2:c.-31+10229C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.96).
• 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 rank	MANE	Protein	UniProt
SLC13A3	NM_001011554.3	c.-31+10229C>T		intron_variant	Intron 2 of 13		NP_001011554.1
SLC13A3	NM_001193340.2	c.-31+10229C>T		intron_variant	Intron 2 of 12		NP_001180269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC13A3	ENST00000417157.2	c.-31+10229C>T		intron_variant	Intron 1 of 3	1		ENSP00000397955.2
SLC13A3	ENST00000290317.9	c.-31+10229C>T		intron_variant	Intron 1 of 12	5		ENSP00000290317.5
SLC13A3	ENST00000472148.5	c.-31+10229C>T		intron_variant	Intron 1 of 11	5		ENSP00000420177.1

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

African (AFR) AF: 0.0296 AC: 1197 AN: 40434

American (AMR) AF: 0.198 AC: 2938 AN: 14846

Ashkenazi Jewish (ASJ) AF: 0.0763 AC: 264 AN: 3462

East Asian (EAS) AF: 0.544 AC: 2783 AN: 5112

South Asian (SAS) AF: 0.284 AC: 1353 AN: 4762

European-Finnish (FIN) AF: 0.142 AC: 1417 AN: 9968

Middle Eastern (MID) AF: 0.136 AC: 39 AN: 286

European-Non Finnish (NFE) AF: 0.133 AC: 8998 AN: 67770

Other (OTH) AF: 0.152 AC: 316 AN: 2084

Alfa AF: 0.135 Hom.: 5476

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
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6066043; hg19: chr20-45288453;