rs112530678

Variant summary

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

The NM_001012755.5(SLC25A53):​c.376G>T​(p.Val126Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,210,107 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.0000046 ( 0 hom. 2 hem. )

Consequence

SLC25A53
NM_001012755.5 missense

Scores

14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.203
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=0.0910455).
BS2
High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC25A53NM_001012755.5 linkc.376G>T p.Val126Leu missense_variant Exon 2 of 2 ENST00000594199.3 NP_001012773.2 Q5H9E4
SLC25A53XM_005262129.6 linkc.376G>T p.Val126Leu missense_variant Exon 2 of 2 XP_005262186.1 Q5H9E4
SLC25A53XM_011530952.4 linkc.376G>T p.Val126Leu missense_variant Exon 3 of 3 XP_011529254.1 Q5H9E4
SLC25A53XM_011530953.4 linkc.376G>T p.Val126Leu 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.376G>T p.Val126Leu missense_variant Exon 2 of 2 1 NM_001012755.5 ENSP00000468980.1 Q5H9E4

Frequencies

GnomAD3 genomes
AF:
0.00000894
AC:
1
AN:
111885
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34035
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
GnomAD3 exomes
AF:
0.00000546
AC:
1
AN:
183061
Hom.:
0
AF XY:
0.0000148
AC XY:
1
AN XY:
67701
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000722
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:
0.00000455
AC:
5
AN:
1098222
Hom.:
0
Cov.:
32
AF XY:
0.00000550
AC XY:
2
AN XY:
363582
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000662
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000356
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000894
AC:
1
AN:
111885
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34035
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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
6.3
DANN
Benign
0.93
DEOGEN2
Benign
0.062
T
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.56
T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.091
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.66
N
PrimateAI
Benign
0.46
T
Sift4G
Benign
0.37
T
Polyphen
0.0010
B
Vest4
0.061
MutPred
0.48
Loss of glycosylation at S124 (P = 0.1675);
MVP
0.51
ClinPred
0.076
T
GERP RS
2.4
Varity_R
0.062
gMVP
0.55

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: rs112530678; hg19: chrX-103349565; API