chrX-119470067-T-C
Position:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2PP3BP4BP6BS1
The NM_001152.5(SLC25A5):āc.518T>Cā(p.Leu173Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000975 in 1,008,679 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. Variant has been reported in Lovd as Likely benign (no stars).
Frequency
Genomes: š 0.016 ( 0 hom., 0 hem., cov: 21)
Exomes š: 0.00015 ( 0 hom. 0 hem. )
Consequence
SLC25A5
NM_001152.5 missense
NM_001152.5 missense
Scores
9
6
2
Clinical Significance
Conservation
PhyloP100: 7.68
Genes affected
SLC25A5 (HGNC:10991): (solute carrier family 25 member 5) This gene is a member of the mitochondrial carrier subfamily of solute carrier protein genes. The product of this gene functions as a gated pore that translocates ADP from the cytoplasm into the mitochondrial matrix and ATP from the mitochondrial matrix into the cytoplasm. The protein forms a homodimer embedded in the inner mitochondria membrane. Suppressed expression of this gene has been shown to induce apoptosis and inhibit tumor growth. The human genome contains several non-transcribed pseudogenes of this gene.[provided by RefSeq, Jun 2013]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
Multiple lines of computational evidence support a deleterious effect 9: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Cadd, M_CAP, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
BP4
Computational evidence support a benign effect (MetaRNN=0.30138046).
BP6
Variant X-119470067-T-C is Benign according to our data. Variant chrX-119470067-T-C is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0164 (844/51451) while in subpopulation AFR AF= 0.0232 (288/12400). AF 95% confidence interval is 0.021. There are 0 homozygotes in gnomad4. There are 0 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC25A5 | NM_001152.5 | c.518T>C | p.Leu173Pro | missense_variant | 2/4 | ENST00000317881.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC25A5 | ENST00000317881.9 | c.518T>C | p.Leu173Pro | missense_variant | 2/4 | 1 | NM_001152.5 | P1 | |
SLC25A5 | ENST00000460013.1 | n.514T>C | non_coding_transcript_exon_variant | 2/4 | 3 | ||||
SLC25A5 | ENST00000475354.1 | n.395T>C | non_coding_transcript_exon_variant | 2/2 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0164 AC: 844AN: 51456Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0AN XY: 7942
GnomAD3 genomes
AF:
AC:
844
AN:
51456
Hom.:
Cov.:
21
AF XY:
AC XY:
0
AN XY:
7942
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.000145 AC: 139AN: 957228Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 264064
GnomAD4 exome
AF:
AC:
139
AN:
957228
Hom.:
Cov.:
36
AF XY:
AC XY:
0
AN XY:
264064
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0164 AC: 844AN: 51451Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0AN XY: 7945
GnomAD4 genome
AF:
AC:
844
AN:
51451
Hom.:
Cov.:
21
AF XY:
AC XY:
0
AN XY:
7945
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
ExAC
AF:
AC:
161
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Small cell lung carcinoma Pathogenic:1
Pathogenic, no assertion criteria provided | research | Arun Kumar Laboratory, Indian Institute of Science | Jun 15, 2021 | - - |
Lung cancer Pathogenic:1
Pathogenic, no assertion criteria provided | research | Arun Kumar Laboratory, Indian Institute of Science | Jun 15, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at