rs369965341
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001143780.3(SLC25A39):c.701G>T(p.Trp234Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SLC25A39
NM_001143780.3 missense
NM_001143780.3 missense
Scores
12
5
2
Clinical Significance
Conservation
PhyloP100: 7.61
Publications
1 publications found
Genes affected
SLC25A39 (HGNC:24279): (solute carrier family 25 member 39) This gene encodes a member of the SLC25 transporter or mitochondrial carrier family of proteins. Members of this family are encoded by the nuclear genome while their protein products are usually embedded in the inner mitochondrial membrane and exhibit wide-ranging substrate specificity. Although the encoded protein is currently considered an orphan transporter, this protein is related to other carriers known to transport amino acids. This protein may play a role in iron homeostasis. [provided by RefSeq, Mar 2016]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.975
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.0000329 AC: 5AN: 152156Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
5
AN:
152156
Hom.:
Cov.:
33
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:
GnomAD2 exomes AF: 0.0000119 AC: 3AN: 251132 AF XY: 0.00000737 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
251132
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461200Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 726946 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461200
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
726946
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33464
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26130
East Asian (EAS)
AF:
AC:
0
AN:
39692
South Asian (SAS)
AF:
AC:
0
AN:
86236
European-Finnish (FIN)
AF:
AC:
0
AN:
53276
Middle Eastern (MID)
AF:
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111550
Other (OTH)
AF:
AC:
0
AN:
60366
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000329 AC: 5AN: 152156Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74330 show subpopulations
GnomAD4 genome
AF:
AC:
5
AN:
152156
Hom.:
Cov.:
33
AF XY:
AC XY:
2
AN XY:
74330
show subpopulations
African (AFR)
AF:
AC:
5
AN:
41438
American (AMR)
AF:
AC:
0
AN:
15266
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5190
South Asian (SAS)
AF:
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68036
Other (OTH)
AF:
AC:
0
AN:
2086
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.455
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
2
ESP6500EA
AF:
AC:
0
ExAC
AF:
AC:
2
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Aug 27, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.701G>T (p.W234L) alteration is located in exon 9 (coding exon 8) of the SLC25A39 gene. This alteration results from a G to T substitution at nucleotide position 701, causing the tryptophan (W) at amino acid position 234 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;T;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
.;L;.;.;.;.
PhyloP100
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;.;.;D;.
REVEL
Pathogenic
Sift
Pathogenic
D;D;.;.;D;.
Sift4G
Pathogenic
D;D;D;D;D;D
Polyphen
D;D;D;.;D;.
Vest4
MVP
MPC
0.41
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
Publications
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