17-44320056-T-C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001143780.3(SLC25A39):​c.1025A>G​(p.Glu342Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SLC25A39
NM_001143780.3 missense

Scores

12
6
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.87

Publications

0 publications found
Variant links:
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]

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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, 0.987

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC25A39NM_001143780.3 linkc.1025A>G p.Glu342Gly missense_variant Exon 12 of 12 ENST00000377095.10 NP_001137252.1 Q9BZJ4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC25A39ENST00000377095.10 linkc.1025A>G p.Glu342Gly missense_variant Exon 12 of 12 1 NM_001143780.3 ENSP00000366299.4 Q9BZJ4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 13, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.1025A>G (p.E342G) alteration is located in exon 12 (coding exon 11) of the SLC25A39 gene. This alteration results from a A to G substitution at nucleotide position 1025, causing the glutamic acid (E) at amino acid position 342 to be replaced by a glycine (G). 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
Pathogenic
0.95
BayesDel_addAF
Pathogenic
0.46
D
BayesDel_noAF
Pathogenic
0.42
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.52
.;D;.;.;.;.
Eigen
Pathogenic
0.71
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.93
.;D;D;D;D;D
M_CAP
Pathogenic
0.30
D
MetaRNN
Pathogenic
0.99
D;D;D;D;D;D
MetaSVM
Uncertain
0.77
D
MutationAssessor
Pathogenic
3.0
.;M;.;.;.;.
PhyloP100
5.9
PrimateAI
Uncertain
0.69
T
PROVEAN
Pathogenic
-6.2
D;D;.;.;D;.
REVEL
Pathogenic
0.96
Sift
Pathogenic
0.0
D;D;.;.;D;.
Sift4G
Pathogenic
0.0
D;D;D;D;D;D
Polyphen
1.0
D;D;D;.;D;.
Vest4
0.91
MutPred
0.92
.;Gain of sheet (P = 0.0827);.;.;.;.;
MVP
0.96
MPC
0.35
ClinPred
1.0
D
GERP RS
5.0
Varity_R
0.78
gMVP
0.86

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

Other links and lift over

hg19: chr17-42397424; API