rs6012006

Variant names:

• chr20-46676386-A-C
• rs6012006
• NM_001011554.3:c.-127-6247T>G

Your query was ambiguous. Multiple possible variants found:

• chr20-46676386-A-C
• chr20-46676386-A-T

Variant summary

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

The NM_001011554.3(SLC13A3):​c.-127-6247T>G variant causes a intron change. 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 0.72 (38452 hom., cov: 20)
• Consequence: SLC13A3 NM_001011554.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: No conservation score assigned
• 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: STRONG, LIMITED Submitted by: PanelApp Australia, Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A3	NM_001011554.3		c.-127-6247T>G		intron	N/A	NP_001011554.1	Q8WWT9-6
	SLC13A3	NM_001193340.2		c.-127-6247T>G		intron	N/A	NP_001180269.1	Q8WWT9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A3	ENST00000372121.5	TSL:5	c.-31+8010T>G		intron	N/A	ENSP00000361193.2	A0A0A0MRQ6

Frequencies

GnomAD3 genomes AF: 0.724 AC: 103707 AN: 143210 Hom.: 38407 Cov.: 20

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.724 AC: 103799 AN: 143294 Hom.: 38452 Cov.: 20 AF XY: 0.719 AC XY: 49808 AN XY: 69232

African (AFR) AF: 0.907 AC: 34782 AN: 38368

American (AMR) AF: 0.627 AC: 8923 AN: 14228

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2158 AN: 3398

East Asian (EAS) AF: 0.459 AC: 2157 AN: 4702

South Asian (SAS) AF: 0.613 AC: 2605 AN: 4252

European-Finnish (FIN) AF: 0.692 AC: 6143 AN: 8874

Middle Eastern (MID) AF: 0.646 AC: 177 AN: 274

European-Non Finnish (NFE) AF: 0.677 AC: 44896 AN: 66324

Other (OTH) AF: 0.670 AC: 1324 AN: 1976

Alfa AF: 0.706 Hom.: 4445

Bravo AF: 0.724

Asia WGS AF: 0.578 AC: 2009 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.38
PromoterAI		-0.011	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6012006;

hg19: chr20-45305025;

COSMIC: COSV71977340;