Variant chr19-6442124-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024103.3(SLC25A23):c.1258G>T(p.Gly420Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,598,628 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

SLC25A23
NM_024103.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.88

Variant links:

Genes affected

SLC25A23 (HGNC:19375): (solute carrier family 25 member 23) Predicted to enable ATP transmembrane transporter activity. Involved in calcium import into the mitochondrion; positive regulation of mitochondrial calcium ion concentration; and regulation of cellular hyperosmotic salinity response. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

SLC25A23 links:

SLC25A23 (HGNC:):

SLC25A23 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A23	NM_024103.3 linkuse as main transcript	c.1258G>T	p.Gly420Cys	missense_variant	10/10	ENST00000301454.9	NP_077008.2	Q9BV35-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A23	ENST00000301454.9 linkuse as main transcript	c.1258G>T	p.Gly420Cys	missense_variant	10/10	1	NM_024103.3	ENSP00000301454.3		Q9BV35-1

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151902

Hom.:

Cov.:

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000572

AC:

AN:

227360

Hom.:

AF XY:

0.0000569

AC XY:

AN XY:

123102

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000128

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000140

AC:

203

AN:

1446726

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

718366

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

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:

0.0000191

Gnomad4 NFE exome

AF:

0.000177

Gnomad4 OTH exome

AF:

0.0000837

GnomAD4 genome

AF:

0.0000461

AC:

AN:

151902

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74208

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:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000138

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000577

AC:

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 19, 2022

The c.1258G>T (p.G420C) alteration is located in exon 10 (coding exon 10) of the SLC25A23 gene. This alteration results from a G to T substitution at nucleotide position 1258, causing the glycine (G) at amino acid position 420 to be replaced by a cysteine (C). 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

0.26

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.61

Eigen

Benign

0.11

Eigen_PC

Benign

-0.058

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.25

MetaRNN

Uncertain

0.64

MetaSVM

Uncertain

0.15

MutationAssessor

Uncertain

2.5

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-4.9

REVEL

Uncertain

0.53

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.46

MutPred

0.62

Gain of catalytic residue at M418 (P = 6e-04);

MVP

0.69

MPC

0.95

ClinPred

0.94

GERP RS

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.48

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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