rs3821093

chr2-171838077-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.84).
• 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/exons	MANE	UniProt
SLC25A12	NM_003705.5	c.466-810G>A		intron_variant		ENST00000422440.7
SLC25A12	XM_047446142.1	c.193-810G>A		intron_variant
SLC25A12	NR_047549.2	n.380-810G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A12	ENST00000422440.7	c.466-810G>A		intron_variant		1	NM_003705.5	P1
SLC25A12	ENST00000263812.8	c.*86-810G>A		intron_variant, NMD_transcript_variant		2
SLC25A12	ENST00000426896.5	c.570-810G>A		intron_variant, NMD_transcript_variant		2
SLC25A12	ENST00000475360.6	c.*183-810G>A		intron_variant, NMD_transcript_variant		5

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

Gnomad4 AFR AF: 0.0856

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.218

Alfa AF: 0.223 Hom.: 506

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

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: rs3821093; hg19: chr2-172694587;