rs6752812

Variant names:

• chr2-171986588-C-A
• rs6752812
• ENST00000464063.1:n.181+13091G>T

Variant summary

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

The ENST00000464063.1(SLC25A12):​n.181+13091G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,008 control chromosomes in the GnomAD database, including 6,222 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 0.28 (6222 hom., cov: 33)
• Consequence: SLC25A12 ENST00000464063.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303
• Publications: 7 publications found

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]

SLC25A12 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 39

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

LOC124905590 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000464063.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A12	ENST00000464063.1	TSL:4	n.181+13091G>T		intron	N/A
	SLC25A12	ENST00000472748.5	TSL:3	n.177+13091G>T		intron	N/A
	SLC25A12	ENST00000484227.5	TSL:4	n.210+4759G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42805 AN: 151888 Hom.: 6219 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.282 AC: 42821 AN: 152008 Hom.: 6222 Cov.: 33 AF XY: 0.275 AC XY: 20445 AN XY: 74306

African (AFR) AF: 0.270 AC: 11207 AN: 41446

American (AMR) AF: 0.262 AC: 4003 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1179 AN: 3464

East Asian (EAS) AF: 0.190 AC: 987 AN: 5182

South Asian (SAS) AF: 0.183 AC: 883 AN: 4828

European-Finnish (FIN) AF: 0.232 AC: 2447 AN: 10526

Middle Eastern (MID) AF: 0.279 AC: 81 AN: 290

European-Non Finnish (NFE) AF: 0.312 AC: 21173 AN: 67968

Other (OTH) AF: 0.286 AC: 602 AN: 2106

Alfa AF: 0.297 Hom.: 3093

Bravo AF: 0.284

Asia WGS AF: 0.227 AC: 789 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.53
PhyloP100		-0.30

Splicing

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

Other links and lift over

dbSNP: rs6752812; hg19: chr2-172851502;