NM_003705.5:c.1745-58A>G

Variant names:

• chr2-171787719-T-C
• rs2292813
• NM_003705.5:c.1745-58A>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.1745-58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 1,608,480 control chromosomes in the GnomAD database, including 641,240 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 (51940 hom., cov: 32)
  • Exomes 𝑓: 0.90 (589300 hom.)
• Consequence: SLC25A12 NM_003705.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.694
• Publications: 37 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A12	NM_003705.5	MANE Select	c.1745-58A>G		intron	N/A	NP_003696.2
	SLC25A12	NR_047549.2		n.1659-58A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A12	ENST00000422440.7	TSL:1 MANE Select	c.1745-58A>G		intron	N/A	ENSP00000388658.2	O75746-1
	SLC25A12	ENST00000958780.1		c.1922-58A>G		intron	N/A	ENSP00000628839.1
	SLC25A12	ENST00000958781.1		c.1832-58A>G		intron	N/A	ENSP00000628840.1

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124321 AN: 152006 Hom.: 51928 Cov.: 32

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.843

GnomAD4 exome AF: 0.898 AC: 1307187 AN: 1456356 Hom.: 589300 Cov.: 31 AF XY: 0.898 AC XY: 650773 AN XY: 724962

African (AFR) AF: 0.633 AC: 21084 AN: 33322

American (AMR) AF: 0.719 AC: 32159 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 23658 AN: 26098

East Asian (EAS) AF: 0.907 AC: 35981 AN: 39664

South Asian (SAS) AF: 0.852 AC: 73406 AN: 86126

European-Finnish (FIN) AF: 0.888 AC: 47433 AN: 53416

Middle Eastern (MID) AF: 0.903 AC: 5197 AN: 5754

European-Non Finnish (NFE) AF: 0.917 AC: 1015066 AN: 1107096

Other (OTH) AF: 0.884 AC: 53203 AN: 60182

GnomAD4 genome AF: 0.818 AC: 124371 AN: 152124 Hom.: 51940 Cov.: 32 AF XY: 0.818 AC XY: 60808 AN XY: 74360

African (AFR) AF: 0.642 AC: 26630 AN: 41450

American (AMR) AF: 0.759 AC: 11600 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 3139 AN: 3472

East Asian (EAS) AF: 0.911 AC: 4707 AN: 5168

South Asian (SAS) AF: 0.844 AC: 4063 AN: 4814

European-Finnish (FIN) AF: 0.887 AC: 9398 AN: 10592

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

European-Non Finnish (NFE) AF: 0.911 AC: 61966 AN: 68016

Other (OTH) AF: 0.837 AC: 1770 AN: 2114

Alfa AF: 0.866 Hom.: 13170

Bravo AF: 0.802

Asia WGS AF: 0.851 AC: 2961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.44
PhyloP100		0.69
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: rs2292813; hg19: chr2-172644229;