Variant X-104104661-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001012755.5(SLC25A53):c.597C>G(p.Ile199Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,209,807 control chromosomes in the GnomAD database, including 1 homozygotes. There are 541 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., 28 hem., cov: 23)

Exomes 𝑓: 0.0013 ( 1 hom. 513 hem. )

Consequence

SLC25A53
NM_001012755.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.252

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009632975).

BS2

High Hemizygotes in GnomAd4 at 28 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A53	NM_001012755.5 linkuse as main transcript	c.597C>G	p.Ile199Met	missense_variant	2/2	ENST00000594199.3	NP_001012773.2	Q5H9E4
SLC25A53	XM_005262129.6 linkuse as main transcript	c.597C>G	p.Ile199Met	missense_variant	2/2		XP_005262186.1	Q5H9E4
SLC25A53	XM_011530952.4 linkuse as main transcript	c.597C>G	p.Ile199Met	missense_variant	3/3		XP_011529254.1	Q5H9E4
SLC25A53	XM_011530953.4 linkuse as main transcript	c.597C>G	p.Ile199Met	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.597C>G	p.Ile199Met	missense_variant	2/2	1	NM_001012755.5	ENSP00000468980.1		Q5H9E4

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

113

AN:

111559

Hom.:

Cov.:

AF XY:

0.000830

AC XY:

AN XY:

33745

show subpopulations

Gnomad AFR

AF:

0.0000979

Gnomad AMI

AF:

0.00146

Gnomad AMR

AF:

0.00104

Gnomad ASJ

AF:

0.00226

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000755

Gnomad FIN

AF:

0.000166

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00164

Gnomad OTH

AF:

0.00133

GnomAD3 exomes

AF:

0.00111

AC:

203

AN:

183084

Hom.:

AF XY:

0.00127

AC XY:

AN XY:

67712

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000547

Gnomad ASJ exome

AF:

0.00549

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.000524

Gnomad FIN exome

AF:

0.000188

Gnomad NFE exome

AF:

0.00157

Gnomad OTH exome

AF:

0.00111

GnomAD4 exome

AF:

0.00135

AC:

1482

AN:

1098192

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

513

AN XY:

363550

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.000767

Gnomad4 ASJ exome

AF:

0.00511

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.000609

Gnomad4 FIN exome

AF:

0.000271

Gnomad4 NFE exome

AF:

0.00149

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00101

AC:

113

AN:

111615

Hom.:

Cov.:

AF XY:

0.000828

AC XY:

AN XY:

33811

show subpopulations

Gnomad4 AFR

AF:

0.0000977

Gnomad4 AMR

AF:

0.00104

Gnomad4 ASJ

AF:

0.00226

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000756

Gnomad4 FIN

AF:

0.000166

Gnomad4 NFE

AF:

0.00164

Gnomad4 OTH

AF:

0.00131

Alfa

AF:

0.00200

Hom.:

Bravo

AF:

0.00127

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00138

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00238

AC:

ExAC

AF:

0.00105

AC:

128

EpiCase

AF:

0.00251

EpiControl

AF:

0.00154

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

Mar 29, 2022

The c.597C>G (p.I199M) alteration is located in exon 2 (coding exon 1) of the SLC25A53 gene. This alteration results from a C to G substitution at nucleotide position 597, causing the isoleucine (I) at amino acid position 199 to be replaced by a methionine (M). 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

0.22

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0096

MetaSVM

Benign

-0.54

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.47

Sift4G

Benign

0.15

Polyphen

0.0060

Vest4

0.12

MVP

0.23

ClinPred

0.0096

GERP RS

3.2

Varity_R

0.21

gMVP

0.56

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