chrX-130367513-G-T

Variant names:

• chrX-130367513-G-T
• rs5977248
• NM_001282195.2:c.855+1837G>T

Variant summary

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

The NM_001282195.2(SLC25A14):​c.855+1837G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 110,283 control chromosomes in the GnomAD database, including 6,535 homozygotes. There are 12,509 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 0.40 (6535 hom., 12509 hem., cov: 22)
• Consequence: SLC25A14 NM_001282195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202
• Publications: 2 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=-0.89).
• 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.855+1837G>T		intron_variant	Intron 9 of 10	ENST00000545805.6	NP_001269124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A14	ENST00000545805.6	c.855+1837G>T		intron_variant	Intron 9 of 10	5	NM_001282195.2	ENSP00000444642.2

Frequencies

GnomAD3 genomes AF: 0.402 AC: 44258 AN: 110226 Hom.: 6539 Cov.: 22

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.401 AC: 44246 AN: 110283 Hom.: 6535 Cov.: 22 AF XY: 0.383 AC XY: 12509 AN XY: 32621

African (AFR) AF: 0.359 AC: 10882 AN: 30319

American (AMR) AF: 0.368 AC: 3811 AN: 10360

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1071 AN: 2637

East Asian (EAS) AF: 0.378 AC: 1309 AN: 3465

South Asian (SAS) AF: 0.411 AC: 1053 AN: 2565

European-Finnish (FIN) AF: 0.321 AC: 1884 AN: 5862

Middle Eastern (MID) AF: 0.427 AC: 90 AN: 211

European-Non Finnish (NFE) AF: 0.443 AC: 23337 AN: 52696

Other (OTH) AF: 0.387 AC: 581 AN: 1502

Alfa AF: 0.431 Hom.: 53543

Bravo AF: 0.405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.81
DANN	Benign	0.30
PhyloP100		-0.20
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: rs5977248; hg19: chrX-129501487;