X-130365856-G-A

Variant names:

• chrX-130365856-G-A
• rs16999665
• NM_001282195.2:c.855+180G>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.855+180G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0305 in 112,115 control chromosomes in the GnomAD database, including 113 homozygotes. There are 938 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 0.031 (113 hom., 938 hem., cov: 23)
• Consequence: SLC25A14 NM_001282195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0982 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A14	NM_001282195.2	MANE Select	c.855+180G>A		intron	N/A	NP_001269124.1
	SLC25A14	NM_001282197.2		c.939+180G>A		intron	N/A	NP_001269126.1
	SLC25A14	NM_001282196.2		c.846+180G>A		intron	N/A	NP_001269125.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A14	ENST00000545805.6	TSL:5 MANE Select	c.855+180G>A		intron	N/A	ENSP00000444642.2
	SLC25A14	ENST00000339231.3	TSL:1	c.939+180G>A		intron	N/A	ENSP00000342797.3
	SLC25A14	ENST00000218197.9	TSL:1	c.855+180G>A		intron	N/A	ENSP00000218197.5

Frequencies

GnomAD3 genomes AF: 0.0306 AC: 3427 AN: 112061 Hom.: 114 Cov.: 23

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.000378

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000369

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0252

Gnomad NFE AF: 0.00137

Gnomad OTH AF: 0.0314

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

GnomAD4 genome AF: 0.0305 AC: 3424 AN: 112115 Hom.: 113 Cov.: 23 AF XY: 0.0273 AC XY: 938 AN XY: 34305

African (AFR) AF: 0.101 AC: 3119 AN: 30835

American (AMR) AF: 0.0168 AC: 178 AN: 10617

Ashkenazi Jewish (ASJ) AF: 0.000378 AC: 1 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3588

South Asian (SAS) AF: 0.000370 AC: 1 AN: 2700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6104

Middle Eastern (MID) AF: 0.0229 AC: 5 AN: 218

European-Non Finnish (NFE) AF: 0.00137 AC: 73 AN: 53203

Other (OTH) AF: 0.0310 AC: 47 AN: 1518

Alfa AF: 0.0241 Hom.: 80

Bravo AF: 0.0363

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.18
PhyloP100		0.13
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: rs16999665; hg19: chrX-129499830;