X-104104870-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001012755.5(SLC25A53):​c.388G>A​(p.Val130Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 1,210,069 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 22)
Exomes 𝑓: 0.0000064 ( 0 hom. 2 hem. )

Consequence

SLC25A53
NM_001012755.5 missense

Scores

1
4
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.694
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.21684587).
BS2
High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC25A53NM_001012755.5 linkc.388G>A p.Val130Met missense_variant Exon 2 of 2 ENST00000594199.3 NP_001012773.2 Q5H9E4
SLC25A53XM_005262129.6 linkc.388G>A p.Val130Met missense_variant Exon 2 of 2 XP_005262186.1 Q5H9E4
SLC25A53XM_011530952.4 linkc.388G>A p.Val130Met missense_variant Exon 3 of 3 XP_011529254.1 Q5H9E4
SLC25A53XM_011530953.4 linkc.388G>A p.Val130Met missense_variant Exon 3 of 3 XP_011529255.1 Q5H9E4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC25A53ENST00000594199.3 linkc.388G>A p.Val130Met missense_variant Exon 2 of 2 1 NM_001012755.5 ENSP00000468980.1 Q5H9E4

Frequencies

GnomAD3 genomes
AF:
0.00000894
AC:
1
AN:
111813
Hom.:
0
Cov.:
22
AF XY:
0.0000294
AC XY:
1
AN XY:
33977
show subpopulations
Gnomad AFR
AF:
0.0000325
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000546
AC:
1
AN:
183080
Hom.:
0
AF XY:
0.0000148
AC XY:
1
AN XY:
67712
show subpopulations
Gnomad AFR exome
AF:
0.0000766
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000637
AC:
7
AN:
1098205
Hom.:
0
Cov.:
32
AF XY:
0.00000550
AC XY:
2
AN XY:
363569
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000331
Gnomad4 SAS exome
AF:
0.0000369
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000475
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000894
AC:
1
AN:
111864
Hom.:
0
Cov.:
22
AF XY:
0.0000294
AC XY:
1
AN XY:
34038
show subpopulations
Gnomad4 AFR
AF:
0.0000325
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:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
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
Jan 31, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.388G>A (p.V130M) 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 388, causing the valine (V) at amino acid position 130 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
0.10
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
T
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.78
T
M_CAP
Pathogenic
0.31
D
MetaRNN
Benign
0.22
T
MetaSVM
Benign
-0.46
T
MutationAssessor
Benign
2.0
M
PrimateAI
Uncertain
0.64
T
Sift4G
Uncertain
0.016
D
Polyphen
0.32
B
Vest4
0.39
MutPred
0.56
Gain of sheet (P = 0.1945);
MVP
0.55
ClinPred
0.12
T
GERP RS
3.3
Varity_R
0.21
gMVP
0.52

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.

Other links and lift over

dbSNP: rs782749042; hg19: chrX-103349553; API