X-130363142-A-G

Variant names:

• chrX-130363142-A-G
• rs12557276
• NM_001282195.2:c.595-1486A>G

Variant summary

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

The NM_001282195.2(SLC25A14):​c.595-1486A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 111,248 control chromosomes in the GnomAD database, including 5,194 homozygotes. There are 11,039 hemizygotes in GnomAD. 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 0.34 (5194 hom., 11039 hem., cov: 23)
• Consequence: SLC25A14 NM_001282195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.469
• Publications: 1 publications found

Genes affected

SLC25A14 (HGNC:10984): (solute carrier family 25 member 14) Mitochondrial uncoupling proteins (UCP) are members of the larger family of mitochondrial anion carrier proteins (MACP). Uncoupling proteins separate oxidative phosphorylation from ATP synthesis with energy dissipated as heat, also referred to as the mitochondrial proton leak. Uncoupling proteins facilitate the transfer of anions from the inner to the outer mitochondrial membrane and the return transfer of protons from the outer to the inner mitochondrial membrane. They also reduce the mitochondrial membrane potential in mammalian cells. This gene is widely expressed in many tissues with the greatest abundance in brain and testis. Alternative splicing results in multiple transcript variants. A pseudogene of this gene has been defined on chromosome 4. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A14	NM_001282195.2	c.595-1486A>G		intron_variant	Intron 7 of 10	ENST00000545805.6	NP_001269124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A14	ENST00000545805.6	c.595-1486A>G		intron_variant	Intron 7 of 10	5	NM_001282195.2	ENSP00000444642.2

Frequencies

GnomAD3 genomes AF: 0.339 AC: 37675 AN: 111197 Hom.: 5200 Cov.: 23

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.338 AC: 37657 AN: 111248 Hom.: 5194 Cov.: 23 AF XY: 0.330 AC XY: 11039 AN XY: 33490

African (AFR) AF: 0.146 AC: 4485 AN: 30769

American (AMR) AF: 0.336 AC: 3512 AN: 10464

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1071 AN: 2638

East Asian (EAS) AF: 0.374 AC: 1314 AN: 3512

South Asian (SAS) AF: 0.403 AC: 1072 AN: 2657

European-Finnish (FIN) AF: 0.325 AC: 1920 AN: 5902

Middle Eastern (MID) AF: 0.399 AC: 85 AN: 213

European-Non Finnish (NFE) AF: 0.443 AC: 23462 AN: 52907

Other (OTH) AF: 0.331 AC: 499 AN: 1508

Alfa AF: 0.381 Hom.: 2586

Bravo AF: 0.332

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.76
PhyloP100		0.47
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: rs12557276; hg19: chrX-129497116;