Variant X-104104915-C-T 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_001012755.5(SLC25A53):c.343G>A(p.Gly115Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000897 in 111,542 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

SLC25A53
NM_001012755.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0900

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 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=0.09000713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A53	NM_001012755.5 linkuse as main transcript	c.343G>A	p.Gly115Arg	missense_variant	2/2	ENST00000594199.3	NP_001012773.2	Q5H9E4
SLC25A53	XM_005262129.6 linkuse as main transcript	c.343G>A	p.Gly115Arg	missense_variant	2/2		XP_005262186.1	Q5H9E4
SLC25A53	XM_011530952.4 linkuse as main transcript	c.343G>A	p.Gly115Arg	missense_variant	3/3		XP_011529254.1	Q5H9E4
SLC25A53	XM_011530953.4 linkuse as main transcript	c.343G>A	p.Gly115Arg	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.343G>A	p.Gly115Arg	missense_variant	2/2	1	NM_001012755.5	ENSP00000468980.1		Q5H9E4

Frequencies

GnomAD3 genomes

AF:

0.00000897

AC:

AN:

111542

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33698

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:

0.00

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

9.11e-7

AC:

AN:

1098220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363580

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:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000897

AC:

AN:

111542

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33698

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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, 2023

The c.343G>A (p.G115R) alteration is located in exon 2 (coding exon 1) of the SLC25A53 gene. This alteration results from a G to A substitution at nucleotide position 343, causing the glycine (G) at amino acid position 115 to be replaced by an arginine (R). 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

0.12

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.062

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.67

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.090

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.39

Sift4G

Benign

0.063

Polyphen

0.0

Vest4

0.098

MutPred

0.45

Gain of methylation at G115 (P = 0.0336);

MVP

0.69

ClinPred

0.046

GERP RS

2.2

Varity_R

0.31

gMVP

0.78

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