rs6017968

Variant names:

• chr20-46677687-T-C
• rs6017968
• NM_001011554.3:c.-128+6709A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001011554.3(SLC13A3):​c.-128+6709A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 152,212 control chromosomes in the GnomAD database, including 27 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 0.010 (27 hom., cov: 32)
• Consequence: SLC13A3 NM_001011554.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193
• 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=-0.93).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0102 (1559/152212) while in subpopulation AFR AF = 0.0351 (1457/41536). AF 95% confidence interval is 0.0336. There are 27 homozygotes in GnomAd4. There are 732 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011554.3. 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_001011554.3		c.-128+6709A>G		intron	N/A	NP_001011554.1
	SLC13A3	NM_001193340.2		c.-128+6709A>G		intron	N/A	NP_001180269.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A3	ENST00000372121.5	TSL:5	c.-31+6709A>G		intron	N/A	ENSP00000361193.2

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1549 AN: 152094 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00812

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

GnomAD4 genome AF: 0.0102 AC: 1559 AN: 152212 Hom.: 27 Cov.: 32 AF XY: 0.00983 AC XY: 732 AN XY: 74438

African (AFR) AF: 0.0351 AC: 1457 AN: 41536

American (AMR) AF: 0.00497 AC: 76 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68006

Other (OTH) AF: 0.00803 AC: 17 AN: 2116

Alfa AF: 0.0108 Hom.: 3

Bravo AF: 0.0109

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.39
PhyloP100		-0.19

Splicing

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

Other links and lift over

dbSNP: rs6017968; hg19: chr20-45306326;