Variant 14-100328843-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_207117.4(SLC25A47):c.445C>T(p.Pro149Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000955 in 1,612,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

SLC25A47
NM_207117.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.391

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051938385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A47	NM_207117.4 linkuse as main transcript	c.445C>T	p.Pro149Ser	missense_variant	5/6	ENST00000361529.5	NP_997000.2
SLC25A47	NM_001350877.2 linkuse as main transcript	c.7C>T	p.Pro3Ser	missense_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.445C>T	p.Pro149Ser	missense_variant	5/6	1	NM_207117.4	ENSP00000354886	P1	Q6Q0C1-1
SLC25A47	ENST00000557052.1 linkuse as main transcript	c.7C>T	p.Pro3Ser	missense_variant	5/6	1		ENSP00000451078

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152276

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.0000897

AC:

AN:

245176

Hom.:

AF XY:

0.0000523

AC XY:

AN XY:

133908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

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:

0.000137

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000986

AC:

144

AN:

1460132

Hom.:

Cov.:

AF XY:

0.0000881

AC XY:

AN XY:

726396

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000117

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.000158

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000908

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Dec 13, 2023

The c.445C>T (p.P149S) alteration is located in exon 5 (coding exon 5) of the SLC25A47 gene. This alteration results from a C to T substitution at nucleotide position 445, causing the proline (P) at amino acid position 149 to be replaced by a serine (S). 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

0.076

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.27

CADD

Benign

8.9

DANN

Benign

0.81

DEOGEN2

Benign

0.020

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.49

T;T

M_CAP

Benign

0.042

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.46

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.42

N;N

REVEL

Benign

0.18

Sift

Benign

0.20

T;D

Sift4G

Benign

0.18

T;D

Polyphen

0.030

B;.

Vest4

0.17

MVP

0.27

MPC

0.25

ClinPred

0.056

GERP RS

2.4

Varity_R

0.028

gMVP

0.44

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

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