3-39383738-C-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_017875.4(SLC25A38):c.14C>G(p.Ser5Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,824 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 Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
SLC25A38
NM_017875.4 stop_gained
NM_017875.4 stop_gained
Scores
2
3
2
Clinical Significance
Conservation
PhyloP100: 2.09
Genes affected
SLC25A38 (HGNC:26054): (solute carrier family 25 member 38) This gene is a member of the mitochondrial carrier family. The encoded protein is required during erythropoiesis and is important for the biosynthesis of heme. Mutations in this gene are the cause of autosomal congenital sideroblastic anemia (anemia, sideroblastic, 2, pyridoxine-refractory). A related pseudogene is found on chromosome 1. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 40 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 3-39383738-C-G is Pathogenic according to our data. Variant chr3-39383738-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 2961574.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC25A38 | NM_017875.4 | c.14C>G | p.Ser5Ter | stop_gained | 1/7 | ENST00000650617.1 | |
LOC105377644 | XR_007096252.1 | n.85+503G>C | intron_variant, non_coding_transcript_variant | ||||
SLC25A38 | NM_001354798.2 | c.14C>G | p.Ser5Ter | stop_gained | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC25A38 | ENST00000650617.1 | c.14C>G | p.Ser5Ter | stop_gained | 1/7 | NM_017875.4 | P1 | ||
ENST00000655387.1 | n.60+503G>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250934Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135758
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461824Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727222
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GnomAD4 genome ? Cov.: 33
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Bravo
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 17, 2023 | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with SLC25A38-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Ser5*) in the SLC25A38 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC25A38 are known to be pathogenic (PMID: 19412178, 25985931). - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at