rs2292813

Variant names:

• chr2-171787719-T-C
• rs2292813
• NM_003705.5:c.1745-58A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-171787719-T-C
• chr2-171787719-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003705.5(SLC25A12):​c.1745-58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 1,608,480 control chromosomes in the GnomAD database, including 641,240 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 0.82 (51940 hom., cov: 32)
  • Exomes 𝑓: 0.90 (589300 hom.)
• Consequence: SLC25A12 NM_003705.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.694

Genes affected

SLC25A12 (HGNC:10982): (solute carrier family 25 member 12) This gene encodes a calcium-binding mitochondrial carrier protein. The encoded protein localizes to the mitochondria and is involved in the exchange of aspartate for glutamate across the inner mitochondrial membrane. Polymorphisms in this gene may be associated with autism, and mutations in this gene may also be a cause of global cerebral hypomyelination. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A12	NM_003705.5	c.1745-58A>G		intron_variant	Intron 16 of 17	ENST00000422440.7	NP_003696.2
SLC25A12	XM_047446142.1	c.1472-58A>G		intron_variant	Intron 14 of 15		XP_047302098.1
SLC25A12	NR_047549.2	n.1659-58A>G		intron_variant	Intron 15 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A12	ENST00000422440.7	c.1745-58A>G		intron_variant	Intron 16 of 17	1	NM_003705.5	ENSP00000388658.2
SLC25A12	ENST00000263812.8	n.*1365-58A>G		intron_variant	Intron 15 of 16	2		ENSP00000263812.4
SLC25A12	ENST00000472070.1	n.1155-58A>G		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124321 AN: 152006 Hom.: 51928 Cov.: 32

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.843

GnomAD4 exome AF: 0.898 AC: 1307187 AN: 1456356 Hom.: 589300 Cov.: 31 AF XY: 0.898 AC XY: 650773 AN XY: 724962

Gnomad4 AFR exome AF: 0.633

Gnomad4 AMR exome AF: 0.719

Gnomad4 ASJ exome AF: 0.907

Gnomad4 EAS exome AF: 0.907

Gnomad4 SAS exome AF: 0.852

Gnomad4 FIN exome AF: 0.888

Gnomad4 NFE exome AF: 0.917

Gnomad4 OTH exome AF: 0.884

GnomAD4 genome AF: 0.818 AC: 124371 AN: 152124 Hom.: 51940 Cov.: 32 AF XY: 0.818 AC XY: 60808 AN XY: 74360

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.759

Gnomad4 ASJ AF: 0.904

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.844

Gnomad4 FIN AF: 0.887

Gnomad4 NFE AF: 0.911

Gnomad4 OTH AF: 0.837

Alfa AF: 0.871 Hom.: 12993

Bravo AF: 0.802

Asia WGS AF: 0.851 AC: 2961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs2292813; hg19: chr2-172644229;