Variant X-130349297-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001282195.2(SLC25A14):c.364A>G(p.Ile122Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000917 in 1,090,348 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.2e-7 ( 0 hom. 0 hem. )

Consequence

SLC25A14
NM_001282195.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.95

Variant links:

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]

SLC25A14 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A14	NM_001282195.2 linkuse as main transcript	c.364A>G	p.Ile122Val	missense_variant	5/11	ENST00000545805.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A14	ENST00000545805.6 linkuse as main transcript	c.364A>G	p.Ile122Val	missense_variant	5/11	5	NM_001282195.2		O95258-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.17e-7

AC:

AN:

1090348

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

356484

show subpopulations

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:

0.0000218

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Apr 13, 2023

Gene of Uncertain Significance -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;.;T;.;T;.;.

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

D;D;D;D;.;D;.

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.72

D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.15

MutationAssessor

Benign

1.1

.;.;L;.;L;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.93

.;N;N;N;N;N;N

REVEL

Uncertain

0.57

Sift

Uncertain

0.0040

.;D;D;D;D;D;D

Sift4G

Uncertain

0.028

D;D;D;D;D;D;D

Polyphen

0.96

D;.;P;.;P;P;D

Vest4

0.53

MutPred

0.68

.;.;Loss of catalytic residue at I122 (P = 0.0818);Loss of catalytic residue at I122 (P = 0.0818);Loss of catalytic residue at I122 (P = 0.0818);.;.;

MVP

0.88

MPC

1.9

ClinPred

0.85

GERP RS

5.0

Varity_R

0.55

gMVP

0.85

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over