Variant 14-100327227-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207117.4(SLC25A47):c.184A>G(p.Thr62Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SLC25A47
NM_207117.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.24

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16760984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A47	NM_207117.4 linkuse as main transcript	c.184A>G	p.Thr62Ala	missense_variant	4/6	ENST00000361529.5	NP_997000.2
SLC25A47	NM_001350877.2 linkuse as main transcript	c.-255A>G		5_prime_UTR_variant	4/6		NP_001337806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A47	ENST00000361529.5 linkuse as main transcript	c.184A>G	p.Thr62Ala	missense_variant	4/6	1	NM_207117.4	ENSP00000354886	P1	Q6Q0C1-1
SLC25A47	ENST00000557052.1 linkuse as main transcript	c.-255A>G		5_prime_UTR_variant	4/6	1		ENSP00000451078

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1457538

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725322

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

May 02, 2024

The c.184A>G (p.T62A) alteration is located in exon 4 (coding exon 4) of the SLC25A47 gene. This alteration results from a A to G substitution at nucleotide position 184, causing the threonine (T) at amino acid position 62 to be replaced by an alanine (A). 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

0.17

BayesDel_addAF

Uncertain

0.049

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.032

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.69

M_CAP

Benign

0.043

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.53

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.5

REVEL

Benign

0.28

Sift

Benign

0.060

Sift4G

Benign

0.15

Polyphen

0.024

Vest4

0.24

MutPred

0.60

Gain of catalytic residue at S67 (P = 0);

MVP

0.33

MPC

0.26

ClinPred

0.83

GERP RS

4.8

Varity_R

0.27

gMVP

0.54

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