2-171986588-C-A

Position:

• chr2-171986588-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007087296.1(LOC124905590):​n.327+4759G>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,008 control chromosomes in the GnomAD database, including 6,222 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 0.28 (6222 hom., cov: 33)
• Consequence: LOC124905590 XR_007087296.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303

Genes affected

LOC124905590 (HGNC:):

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124905590	XR_007087296.1	n.327+4759G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A12	ENST00000464063.1	n.181+13091G>T		intron_variant, non_coding_transcript_variant		4
SLC25A12	ENST00000472748.5	n.177+13091G>T		intron_variant, non_coding_transcript_variant		3
SLC25A12	ENST00000484227.5	n.210+4759G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42805 AN: 151888 Hom.: 6219 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.282 AC: 42821 AN: 152008 Hom.: 6222 Cov.: 33 AF XY: 0.275 AC XY: 20445 AN XY: 74306

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.286

Alfa AF: 0.295 Hom.: 2661

Bravo AF: 0.284

Asia WGS AF: 0.227 AC: 789 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6752812; hg19: chr2-172851502;