X-130362412-G-C

Variant names:

• chrX-130362412-G-C
• rs6418932
• NM_001282195.2:c.595-2216G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001282195.2(SLC25A14):​c.595-2216G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000915 in 109,240 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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 0.0000092 (0 hom., 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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>C		intron	N/A	NP_001269124.1	O95258-1
	SLC25A14	NM_001282197.2		c.679-2216G>C		intron	N/A	NP_001269126.1	O95258-3
	SLC25A14	NM_001282196.2		c.586-2216G>C		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>C		intron	N/A	ENSP00000444642.2	O95258-1
	SLC25A14	ENST00000339231.3	TSL:1	c.679-2216G>C		intron	N/A	ENSP00000342797.3	O95258-3
	SLC25A14	ENST00000218197.9	TSL:1	c.595-2216G>C		intron	N/A	ENSP00000218197.5	O95258-1

Frequencies

GnomAD3 genomes AF: 0.00000915 AC: 1 AN: 109240 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000190

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000915 AC: 1 AN: 109240 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 31546

African (AFR) AF: 0.00 AC: 0 AN: 29984

American (AMR) AF: 0.00 AC: 0 AN: 10144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2621

East Asian (EAS) AF: 0.00 AC: 0 AN: 3461

South Asian (SAS) AF: 0.00 AC: 0 AN: 2572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5517

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000190 AC: 1 AN: 52598

Other (OTH) AF: 0.00 AC: 0 AN: 1439

Alfa AF: 0.00 Hom.: 1961

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.51
DANN	Benign	0.46
PhyloP100		0.037

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;