Variant chrX-104105098-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_001012755.5(SLC25A53):c.160C>T(p.Arg54Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,210,657 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000019 ( 0 hom. 7 hem. )

Consequence

SLC25A53
NM_001012755.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.39

Variant links:

Genes affected

SLC25A53 (HGNC:31894): (solute carrier family 25 member 53) Predicted to be located in mitochondrial inner membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC25A53 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.917

BS2

High Hemizygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A53	NM_001012755.5 linkuse as main transcript	c.160C>T	p.Arg54Trp	missense_variant	2/2	ENST00000594199.3	NP_001012773.2	Q5H9E4
SLC25A53	XM_005262129.6 linkuse as main transcript	c.160C>T	p.Arg54Trp	missense_variant	2/2		XP_005262186.1	Q5H9E4
SLC25A53	XM_011530952.4 linkuse as main transcript	c.160C>T	p.Arg54Trp	missense_variant	3/3		XP_011529254.1	Q5H9E4
SLC25A53	XM_011530953.4 linkuse as main transcript	c.160C>T	p.Arg54Trp	missense_variant	3/3		XP_011529255.1	Q5H9E4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A53	ENST00000594199.3 linkuse as main transcript	c.160C>T	p.Arg54Trp	missense_variant	2/2	1	NM_001012755.5	ENSP00000468980.1		Q5H9E4

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112415

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34583

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000278

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000327

AC:

AN:

183489

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

67919

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.0000365

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:

0.0000366

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000191

AC:

AN:

1098242

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

363596

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

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:

0.0000214

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112415

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34583

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000278

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000109

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

Jan 23, 2024

The c.160C>T (p.R54W) alteration is located in exon 2 (coding exon 1) of the SLC25A53 gene. This alteration results from a C to T substitution at nucleotide position 160, causing the arginine (R) at amino acid position 54 to be replaced by a tryptophan (W). 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

Pathogenic

0.58

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.46

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.81

M_CAP

Pathogenic

0.53

MetaRNN

Pathogenic

0.92

MetaSVM

Uncertain

0.74

MutationAssessor

Pathogenic

3.4

PrimateAI

Uncertain

0.75

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.81

MutPred

0.74

Gain of methylation at K50 (P = 0.0728);

MVP

0.21

ClinPred

0.78

GERP RS

4.0

Varity_R

0.77

gMVP

0.98

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