2-171855970-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003705.5(SLC25A12):c.210-21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 1,321,958 control chromosomes in the GnomAD database, including 469,296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (46204 hom., cov: 32)
  • Exomes 𝑓: 0.85 (423092 hom.)
• Consequence: SLC25A12 NM_003705.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.65

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 2-171855970-T-C is Benign according to our data. Variant chr2-171855970-T-C is described in ClinVar as [Benign]. Clinvar id is 1332979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A12	NM_003705.5	c.210-21A>G		intron_variant		ENST00000422440.7
SLC25A12	NR_047549.2	n.240-11462A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A12	ENST00000422440.7	c.210-21A>G		intron_variant		1	NM_003705.5	P1

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117165 AN: 152040 Hom.: 46203 Cov.: 32

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.793

GnomAD3 exomes AF: 0.805 AC: 202129 AN: 250994 Hom.: 82927 AF XY: 0.818 AC XY: 111016 AN XY: 135710

Gnomad AFR exome AF: 0.597

Gnomad AMR exome AF: 0.612

Gnomad ASJ exome AF: 0.872

Gnomad EAS exome AF: 0.892

Gnomad SAS exome AF: 0.834

Gnomad FIN exome AF: 0.819

Gnomad NFE exome AF: 0.863

Gnomad OTH exome AF: 0.820

GnomAD4 exome AF: 0.847 AC: 991242 AN: 1169800 Hom.: 423092 Cov.: 16 AF XY: 0.849 AC XY: 506422 AN XY: 596750

Gnomad4 AFR exome AF: 0.601

Gnomad4 AMR exome AF: 0.618

Gnomad4 ASJ exome AF: 0.872

Gnomad4 EAS exome AF: 0.897

Gnomad4 SAS exome AF: 0.835

Gnomad4 FIN exome AF: 0.824

Gnomad4 NFE exome AF: 0.868

Gnomad4 OTH exome AF: 0.837

GnomAD4 genome AF: 0.770 AC: 117199 AN: 152158 Hom.: 46204 Cov.: 32 AF XY: 0.770 AC XY: 57279 AN XY: 74374

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.868

Gnomad4 EAS AF: 0.894

Gnomad4 SAS AF: 0.829

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.862

Gnomad4 OTH AF: 0.787

Alfa AF: 0.840 Hom.: 27834

Bravo AF: 0.753

Asia WGS AF: 0.825 AC: 2871 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Developmental and epileptic encephalopathy, 39 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	18
Dann	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs2056202; hg19: chr2-172712480;