rs759482927

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001143780.3(SLC25A39):​c.932G>C​(p.Arg311Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,594 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R311Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC25A39
NM_001143780.3 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.39
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC25A39NM_001143780.3 linkc.932G>C p.Arg311Pro missense_variant Exon 11 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.932G>C p.Arg311Pro missense_variant Exon 11 of 12 1 NM_001143780.3 ENSP00000366299.4 Q9BZJ4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461594
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727112
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53134
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1112006
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60394
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

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.62
BayesDel_addAF
Uncertain
0.013
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
0.068
DANN
Benign
0.78
DEOGEN2
Benign
0.15
.;T;.;.;.;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.35
N
LIST_S2
Benign
0.21
.;T;T;T;T;T
M_CAP
Uncertain
0.19
D
MetaRNN
Uncertain
0.52
D;D;D;D;D;D
MetaSVM
Benign
-0.67
T
MutationAssessor
Benign
1.3
.;L;.;.;.;.
PhyloP100
-2.4
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-1.3
N;N;.;.;N;.
REVEL
Uncertain
0.53
Sift
Benign
0.075
T;T;.;.;D;.
Sift4G
Uncertain
0.055
T;T;T;T;T;T
Polyphen
0.57
P;P;P;.;P;.
Vest4
0.64
MutPred
0.74
.;Loss of MoRF binding (P = 0.0047);.;.;.;.;
MVP
0.31
MPC
0.065
ClinPred
0.53
D
GERP RS
-7.6
Varity_R
0.15
gMVP
0.85

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

dbSNP: rs759482927; hg19: chr17-42397596; API