rs2235800

Positions:

• chrX-130364862-T-A
• chrX-130364862-T-C

Variant summary

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

The NM_001282195.2(SLC25A14):​c.719+110T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 1,115,878 control chromosomes in the GnomAD database, including 73,788 homozygotes. There are 149,417 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 0.41 (6769 hom., 12880 hem., cov: 22)
  • Exomes 𝑓: 0.44 (67019 hom. 136537 hem.)
• Consequence: SLC25A14 NM_001282195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A14	NM_001282195.2	c.719+110T>A		intron_variant		ENST00000545805.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A14	ENST00000545805.6	c.719+110T>A		intron_variant		5	NM_001282195.2

Frequencies

GnomAD3 genomes AF: 0.410 AC: 45286 AN: 110588 Hom.: 6773 Cov.: 22 AF XY: 0.392 AC XY: 12866 AN XY: 32856

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.426

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.400

GnomAD4 exome AF: 0.439 AC: 441241 AN: 1005236 Hom.: 67019 Cov.: 22 AF XY: 0.445 AC XY: 136537 AN XY: 306706

Gnomad4 AFR exome AF: 0.391

Gnomad4 AMR exome AF: 0.378

Gnomad4 ASJ exome AF: 0.429

Gnomad4 EAS exome AF: 0.361

Gnomad4 SAS exome AF: 0.421

Gnomad4 FIN exome AF: 0.369

Gnomad4 NFE exome AF: 0.450

Gnomad4 OTH exome AF: 0.425

GnomAD4 genome AF: 0.409 AC: 45274 AN: 110642 Hom.: 6769 Cov.: 22 AF XY: 0.391 AC XY: 12880 AN XY: 32920

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.394

Alfa AF: 0.424 Hom.: 2876

Bravo AF: 0.414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.62
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2235800; hg19: chrX-129498836; COSMIC: COSV54417883; COSMIC: COSV54417883;