chr20-46649530-A-G

Variant names:

• chr20-46649530-A-G
• rs1004571
• NM_022829.6:c.111+1781T>C

Variant summary

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

The NM_022829.6(SLC13A3):​c.111+1781T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,042 control chromosomes in the GnomAD database, including 40,417 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 0.72 (40417 hom., cov: 31)
• Consequence: SLC13A3 NM_022829.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• Publications: 8 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=-0.91).
• 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_022829.6. 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_022829.6	MANE Select	c.111+1781T>C		intron	N/A	NP_073740.2
	SLC13A3	NM_001011554.3		c.-31+20513T>C		intron	N/A	NP_001011554.1
	SLC13A3	NM_001193339.2		c.111+1781T>C		intron	N/A	NP_001180268.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A3	ENST00000279027.9	TSL:1 MANE Select	c.111+1781T>C		intron	N/A	ENSP00000279027.4
	SLC13A3	ENST00000417157.2	TSL:1	c.-31+20513T>C		intron	N/A	ENSP00000397955.2
	SLC13A3	ENST00000290317.9	TSL:5	c.-31+20513T>C		intron	N/A	ENSP00000290317.5

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109165 AN: 151924 Hom.: 40368 Cov.: 31

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.719 AC: 109273 AN: 152042 Hom.: 40417 Cov.: 31 AF XY: 0.713 AC XY: 52950 AN XY: 74304

African (AFR) AF: 0.907 AC: 37655 AN: 41522

American (AMR) AF: 0.620 AC: 9469 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2170 AN: 3466

East Asian (EAS) AF: 0.453 AC: 2331 AN: 5144

South Asian (SAS) AF: 0.625 AC: 3007 AN: 4810

European-Finnish (FIN) AF: 0.671 AC: 7077 AN: 10548

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45338 AN: 67968

Other (OTH) AF: 0.662 AC: 1394 AN: 2106

Alfa AF: 0.679 Hom.: 116416

Bravo AF: 0.722

Asia WGS AF: 0.588 AC: 2047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.032
DANN	Benign	0.27
PhyloP100		-2.7
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: rs1004571; hg19: chr20-45278169;