X-130359090-T-C

Position:

• chrX-130359090-T-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP6

The ENST00000339231.3(SLC25A14):​c.629T>C​(p.Met210Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: SLC25A14 ENST00000339231.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.303

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

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07886499).
• BP6: Variant X-130359090-T-C is Benign according to our data. Variant chrX-130359090-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2681550.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A14	NM_001282195.2	c.594+355T>C		intron_variant		ENST00000545805.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A14	ENST00000545805.6	c.594+355T>C		intron_variant		5	NM_001282195.2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 799867 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 223845

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

EBV-positive nodal T- and NK-cell lymphoma Benign:1

Likely benign, no assertion criteria provided

research

Department of Clinical Pathology, School of Medicine, Fujita Health University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.9
DANN	Benign	0.19
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.24	T;.
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	1.0	N;N;N;N;N
PROVEAN	Benign	-0.11	.;N
REVEL	Benign	0.090
Sift	Benign	0.96	.;T
Sift4G	Benign	0.25	T;T
Polyphen		0.0	B;B
Vest4		0.34
MutPred		0.48		Loss of stability (P = 0.0151);Loss of stability (P = 0.0151);
MVP		0.10
ClinPred		0.014	T
GERP RS		0.23
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2033883338; hg19: chrX-129493064; COSMIC: COSV104584087; COSMIC: COSV104584087;