rs1400816

Positions:

• chr2-171824168-A-C
• chr2-171824168-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A12	NM_003705.5	c.930+2630T>G		intron_variant		ENST00000422440.7	NP_003696.2
SLC25A12	XM_047446142.1	c.657+2630T>G		intron_variant			XP_047302098.1
SLC25A12	NR_047549.2	n.844+2630T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A12	ENST00000422440.7	c.930+2630T>G		intron_variant		1	NM_003705.5	ENSP00000388658	P1
SLC25A12	ENST00000263812.8	c.*550+2630T>G		intron_variant, NMD_transcript_variant		2		ENSP00000263812
SLC25A12	ENST00000485880.1	n.458+2630T>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.904

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.845

Gnomad4 FIN AF: 0.887

Gnomad4 NFE AF: 0.911

Gnomad4 OTH AF: 0.834

Alfa AF: 0.898 Hom.: 97224

Bravo AF: 0.800

Asia WGS AF: 0.851 AC: 2963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.9
DANN	Benign	0.81

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: rs1400816; hg19: chr2-172680678;