chrX-130364862-T-A

Variant names:

• chrX-130364862-T-A
• rs2235800
• NM_001282195.2:c.719+110T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.9).
• 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 rank	MANE	Protein	UniProt
SLC25A14	NM_001282195.2	c.719+110T>A		intron_variant	Intron 8 of 10	ENST00000545805.6	NP_001269124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A14	ENST00000545805.6	c.719+110T>A		intron_variant	Intron 8 of 10	5	NM_001282195.2	ENSP00000444642.2

Frequencies

GnomAD3 genomes AF: 0.410 AC: 45286 AN: 110588 Hom.: 6773 Cov.: 22

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

African (AFR) AF: 0.391 AC: 9314 AN: 23796

American (AMR) AF: 0.378 AC: 10106 AN: 26758

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 7212 AN: 16818

East Asian (EAS) AF: 0.361 AC: 9053 AN: 25109

South Asian (SAS) AF: 0.421 AC: 20682 AN: 49076

European-Finnish (FIN) AF: 0.369 AC: 10424 AN: 28269

Middle Eastern (MID) AF: 0.364 AC: 1351 AN: 3716

European-Non Finnish (NFE) AF: 0.450 AC: 355518 AN: 790355

Other (OTH) AF: 0.425 AC: 17581 AN: 41339

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

African (AFR) AF: 0.387 AC: 11760 AN: 30414

American (AMR) AF: 0.371 AC: 3873 AN: 10434

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1074 AN: 2636

East Asian (EAS) AF: 0.374 AC: 1316 AN: 3515

South Asian (SAS) AF: 0.406 AC: 1068 AN: 2628

European-Finnish (FIN) AF: 0.321 AC: 1874 AN: 5838

Middle Eastern (MID) AF: 0.433 AC: 93 AN: 215

European-Non Finnish (NFE) AF: 0.443 AC: 23390 AN: 52779

Other (OTH) AF: 0.394 AC: 593 AN: 1505

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
PhyloP100		-0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs2235800; hg19: chrX-129498836; COSMIC: COSV54417883; COSMIC: COSV54417883;