rs5977238

Variant names:

• chrX-130346762-G-A
• rs5977238
• NM_001282195.2:c.317+71G>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.317+71G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 921,805 control chromosomes in the GnomAD database, including 533 homozygotes. There are 2,307 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 0.046 (296 hom., 1327 hem., cov: 22)
  • Exomes 𝑓: 0.0056 (237 hom. 980 hem.)
• Consequence: SLC25A14 NM_001282195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 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.317+71G>A		intron	N/A	NP_001269124.1
	SLC25A14	NM_001282197.2		c.308+71G>A		intron	N/A	NP_001269126.1
	SLC25A14	NM_001282196.2		c.308+71G>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.317+71G>A		intron	N/A	ENSP00000444642.2
	SLC25A14	ENST00000339231.3	TSL:1	c.308+71G>A		intron	N/A	ENSP00000342797.3
	SLC25A14	ENST00000218197.9	TSL:1	c.317+71G>A		intron	N/A	ENSP00000218197.5

Frequencies

GnomAD3 genomes AF: 0.0459 AC: 5133 AN: 111815 Hom.: 296 Cov.: 22

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0224

Gnomad ASJ AF: 0.00152

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00147

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0168

Gnomad NFE AF: 0.000829

Gnomad OTH AF: 0.0455

GnomAD4 exome AF: 0.00560 AC: 4532 AN: 809937 Hom.: 237 AF XY: 0.00510 AC XY: 980 AN XY: 192317

African (AFR) AF: 0.165 AC: 3320 AN: 20148

American (AMR) AF: 0.0110 AC: 309 AN: 27970

Ashkenazi Jewish (ASJ) AF: 0.000978 AC: 15 AN: 15335

East Asian (EAS) AF: 0.00 AC: 0 AN: 28187

South Asian (SAS) AF: 0.000520 AC: 20 AN: 38435

European-Finnish (FIN) AF: 0.0000556 AC: 2 AN: 35981

Middle Eastern (MID) AF: 0.0106 AC: 36 AN: 3386

European-Non Finnish (NFE) AF: 0.000637 AC: 385 AN: 604357

Other (OTH) AF: 0.0123 AC: 445 AN: 36138

GnomAD4 genome AF: 0.0459 AC: 5134 AN: 111868 Hom.: 296 Cov.: 22 AF XY: 0.0389 AC XY: 1327 AN XY: 34128

African (AFR) AF: 0.155 AC: 4773 AN: 30814

American (AMR) AF: 0.0224 AC: 237 AN: 10578

Ashkenazi Jewish (ASJ) AF: 0.00152 AC: 4 AN: 2637

East Asian (EAS) AF: 0.00 AC: 0 AN: 3581

South Asian (SAS) AF: 0.00148 AC: 4 AN: 2706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6012

Middle Eastern (MID) AF: 0.0138 AC: 3 AN: 217

European-Non Finnish (NFE) AF: 0.000829 AC: 44 AN: 53098

Other (OTH) AF: 0.0449 AC: 69 AN: 1536

Alfa AF: 0.0315 Hom.: 176

Bravo AF: 0.0536

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.6
DANN	Benign	0.65
PhyloP100		-0.034
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: rs5977238; hg19: chrX-129480736;