Variant 14-100328772-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_207117.4(SLC25A47):c.374C>A(p.Thr125Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLC25A47
NM_207117.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.07

Variant links:

Genes affected

SLC25A47 (HGNC:20115): (solute carrier family 25 member 47) This gene encodes a member of a large family of mitochondrial transporters. The nuclear-encoded carrier protein is embedded in the inner mitochondrial membrane. This member of the family is thought to be an uncoupling protein that uncouples mitochondrial respiration from ATP synthesis by dissipating the transmembrane proton gradient. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

SLC25A47 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.815

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A47	NM_207117.4 linkuse as main transcript	c.374C>A	p.Thr125Lys	missense_variant	5/6	ENST00000361529.5	NP_997000.2	Q6Q0C1-1A0A024R6H7
SLC25A47	NM_001350877.2 linkuse as main transcript	c.-65C>A		5_prime_UTR_variant	5/6		NP_001337806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A47	ENST00000361529.5 linkuse as main transcript	c.374C>A	p.Thr125Lys	missense_variant	5/6	1	NM_207117.4	ENSP00000354886.3		Q6Q0C1-1
SLC25A47	ENST00000557052.1 linkuse as main transcript	c.-65C>A		5_prime_UTR_variant	5/6	1		ENSP00000451078.1		G3V374

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000408

AC:

AN:

245346

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000918

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460588

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726628

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000193

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2024

The c.374C>A (p.T125K) alteration is located in exon 5 (coding exon 5) of the SLC25A47 gene. This alteration results from a C to A substitution at nucleotide position 374, causing the threonine (T) at amino acid position 125 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.82

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.82

MetaSVM

Uncertain

0.50

MutationAssessor

Uncertain

2.5

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.53

Sift

Benign

0.050

Sift4G

Benign

0.069

Polyphen

0.99

Vest4

0.71

MutPred

0.44

Gain of MoRF binding (P = 0.0394);

MVP

0.79

MPC

0.94

ClinPred

0.95

GERP RS

4.5

Varity_R

0.55

gMVP

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over