2-171987022-C-G

Variant names:

• chr2-171987022-C-G
• rs17428076
• ENST00000464063.1:n.181+12657G>C

Variant summary

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

The ENST00000464063.1(SLC25A12):​n.181+12657G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,000 control chromosomes in the GnomAD database, including 2,778 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 0.18 (2778 hom., cov: 31)
• Consequence: SLC25A12 ENST00000464063.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51
• Publications: 15 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124905590	XR_007087296.1	n.327+4325G>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A12	ENST00000464063.1	n.181+12657G>C		intron_variant	Intron 1 of 4	4
SLC25A12	ENST00000472748.5	n.177+12657G>C		intron_variant	Intron 1 of 4	3
SLC25A12	ENST00000484227.5	n.210+4325G>C		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27274 AN: 151880 Hom.: 2781 Cov.: 31

Gnomad AFR AF: 0.0958

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.0541

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.179 AC: 27256 AN: 152000 Hom.: 2778 Cov.: 31 AF XY: 0.177 AC XY: 13136 AN XY: 74252

African (AFR) AF: 0.0955 AC: 3964 AN: 41498

American (AMR) AF: 0.152 AC: 2320 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 790 AN: 3468

East Asian (EAS) AF: 0.0542 AC: 280 AN: 5168

South Asian (SAS) AF: 0.218 AC: 1050 AN: 4812

European-Finnish (FIN) AF: 0.190 AC: 1998 AN: 10530

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16269 AN: 67952

Other (OTH) AF: 0.185 AC: 388 AN: 2102

Alfa AF: 0.206 Hom.: 411

Bravo AF: 0.172

Asia WGS AF: 0.139 AC: 488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.75
PhyloP100		-2.5

Splicing

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

Other links and lift over

dbSNP: rs17428076; hg19: chr2-172851936;