X-130362412-G-A

Variant names:

• chrX-130362412-G-A
• rs6418932
• NM_001282195.2:c.595-2216G>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.595-2216G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 109,213 control chromosomes in the GnomAD database, including 7,181 homozygotes. There are 12,950 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 0.42 (7181 hom., 12950 hem., cov: 22)
• Consequence: SLC25A14 NM_001282195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282195.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A14	NM_001282195.2	MANE Select	c.595-2216G>A		intron	N/A	NP_001269124.1	O95258-1
	SLC25A14	NM_001282197.2		c.679-2216G>A		intron	N/A	NP_001269126.1	O95258-3
	SLC25A14	NM_001282196.2		c.586-2216G>A		intron	N/A	NP_001269125.1	O95258-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A14	ENST00000545805.6	TSL:5 MANE Select	c.595-2216G>A		intron	N/A	ENSP00000444642.2	O95258-1
	SLC25A14	ENST00000339231.3	TSL:1	c.679-2216G>A		intron	N/A	ENSP00000342797.3	O95258-3
	SLC25A14	ENST00000218197.9	TSL:1	c.595-2216G>A		intron	N/A	ENSP00000218197.5	O95258-1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 46372 AN: 109171 Hom.: 7183 Cov.: 22

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.425 AC: 46380 AN: 109213 Hom.: 7181 Cov.: 22 AF XY: 0.410 AC XY: 12950 AN XY: 31567

African (AFR) AF: 0.434 AC: 13038 AN: 30016

American (AMR) AF: 0.378 AC: 3841 AN: 10151

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1059 AN: 2619

East Asian (EAS) AF: 0.380 AC: 1309 AN: 3449

South Asian (SAS) AF: 0.412 AC: 1057 AN: 2563

European-Finnish (FIN) AF: 0.328 AC: 1805 AN: 5509

Middle Eastern (MID) AF: 0.442 AC: 95 AN: 215

European-Non Finnish (NFE) AF: 0.444 AC: 23350 AN: 52571

Other (OTH) AF: 0.406 AC: 590 AN: 1454

Alfa AF: 0.307 Hom.: 1961

Bravo AF: 0.429

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.58
DANN	Benign	0.40
PhyloP100		0.037
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: rs6418932; hg19: chrX-129496386;