2-171824168-A-C

Variant names:

• chr2-171824168-A-C
• rs1400816
• NM_003705.5:c.930+2630T>G

Variant summary

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

The NM_003705.5(SLC25A12):​c.930+2630T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 152,196 control chromosomes in the GnomAD database, including 51,740 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 0.82 (51740 hom., cov: 31)
• Consequence: SLC25A12 NM_003705.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003705.5. 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
	SLC25A12	NM_003705.5	MANE Select	c.930+2630T>G		intron	N/A	NP_003696.2
	SLC25A12	NR_047549.2		n.844+2630T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A12	ENST00000422440.7	TSL:1 MANE Select	c.930+2630T>G		intron	N/A	ENSP00000388658.2
	SLC25A12	ENST00000263812.8	TSL:2	n.*550+2630T>G		intron	N/A	ENSP00000263812.4
	SLC25A12	ENST00000485880.1	TSL:3	n.458+2630T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124054 AN: 152078 Hom.: 51734 Cov.: 31

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.840

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

GnomAD4 genome AF: 0.815 AC: 124099 AN: 152196 Hom.: 51740 Cov.: 31 AF XY: 0.815 AC XY: 60678 AN XY: 74414

African (AFR) AF: 0.635 AC: 26344 AN: 41460

American (AMR) AF: 0.758 AC: 11603 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 3137 AN: 3470

East Asian (EAS) AF: 0.911 AC: 4725 AN: 5186

South Asian (SAS) AF: 0.845 AC: 4082 AN: 4830

European-Finnish (FIN) AF: 0.887 AC: 9396 AN: 10596

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.911 AC: 61950 AN: 68026

Other (OTH) AF: 0.834 AC: 1763 AN: 2114

Alfa AF: 0.882 Hom.: 235702

Bravo AF: 0.800

Asia WGS AF: 0.851 AC: 2963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.9
DANN	Benign	0.81
PhyloP100		-0.35
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: rs1400816; hg19: chr2-172680678; COSMIC: COSV107231206;