rs3821093

Variant names:

• chr2-171838077-C-T
• rs3821093
• NM_003705.5:c.466-810G>A

Variant summary

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

The NM_003705.5(SLC25A12):​c.466-810G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,068 control chromosomes in the GnomAD database, including 4,146 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 0.21 (4146 hom., cov: 32)
• Consequence: SLC25A12 NM_003705.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 3 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A12	NM_003705.5	c.466-810G>A		intron_variant	Intron 5 of 17	ENST00000422440.7	NP_003696.2
SLC25A12	NR_047549.2	n.380-810G>A		intron_variant	Intron 4 of 16
SLC25A12	XM_047446142.1	c.193-810G>A		intron_variant	Intron 3 of 15		XP_047302098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A12	ENST00000422440.7	c.466-810G>A		intron_variant	Intron 5 of 17	1	NM_003705.5	ENSP00000388658.2
SLC25A12	ENST00000263812.8	n.*86-810G>A		intron_variant	Intron 4 of 16	2		ENSP00000263812.4
SLC25A12	ENST00000426896.5	n.570-810G>A		intron_variant	Intron 6 of 8	2		ENSP00000413968.1
SLC25A12	ENST00000475360.6	n.*183-810G>A		intron_variant	Intron 7 of 7	5		ENSP00000437845.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31959 AN: 151950 Hom.: 4150 Cov.: 32

Gnomad AFR AF: 0.0858

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.210 AC: 31942 AN: 152068 Hom.: 4146 Cov.: 32 AF XY: 0.214 AC XY: 15917 AN XY: 74322

African (AFR) AF: 0.0856 AC: 3552 AN: 41516

American (AMR) AF: 0.171 AC: 2607 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 965 AN: 3466

East Asian (EAS) AF: 0.573 AC: 2959 AN: 5162

South Asian (SAS) AF: 0.305 AC: 1469 AN: 4824

European-Finnish (FIN) AF: 0.268 AC: 2826 AN: 10554

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16902 AN: 67950

Other (OTH) AF: 0.218 AC: 460 AN: 2114

Alfa AF: 0.217 Hom.: 509

Bravo AF: 0.199

Asia WGS AF: 0.357 AC: 1245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.82
DANN	Benign	0.49
PhyloP100		-1.0
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: rs3821093; hg19: chr2-172694587;