10-99620220-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_031212.4(SLC25A28):​c.116G>T​(p.Arg39Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000574 in 1,393,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000032 ( 0 hom. )

Consequence

SLC25A28
NM_031212.4 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.12
Variant links:
Genes affected
SLC25A28 (HGNC:23472): (solute carrier family 25 member 28) Predicted to enable ferrous iron transmembrane transporter activity. Predicted to be involved in iron import into the mitochondrion. Predicted to be located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.16402644).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC25A28NM_031212.4 linkc.116G>T p.Arg39Leu missense_variant Exon 1 of 4 ENST00000370495.6 NP_112489.3 Q96A46-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC25A28ENST00000370495.6 linkc.116G>T p.Arg39Leu missense_variant Exon 1 of 4 1 NM_031212.4 ENSP00000359526.4 Q96A46-1

Frequencies

GnomAD3 genomes
AF:
0.0000265
AC:
4
AN:
151022
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000780
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000336
AC:
1
AN:
29754
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
17278
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000792
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000322
AC:
4
AN:
1242770
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
607808
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000719
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.93e-7
Gnomad4 OTH exome
AF:
0.0000198
GnomAD4 genome
AF:
0.0000265
AC:
4
AN:
151128
Hom.:
0
Cov.:
32
AF XY:
0.0000406
AC XY:
3
AN XY:
73828
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000783
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 02, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.116G>T (p.R39L) alteration is located in exon 1 (coding exon 1) of the SLC25A28 gene. This alteration results from a G to T substitution at nucleotide position 116, causing the arginine (R) at amino acid position 39 to be replaced by a leucine (L). 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
Benign
0.098
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.071
T
Eigen
Benign
-0.28
Eigen_PC
Benign
-0.053
FATHMM_MKL
Benign
0.67
D
LIST_S2
Benign
0.56
T
M_CAP
Pathogenic
0.97
D
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
0.34
N
PrimateAI
Pathogenic
0.97
D
PROVEAN
Benign
0.28
N
REVEL
Benign
0.18
Sift
Uncertain
0.0050
D
Sift4G
Uncertain
0.010
D
Polyphen
0.0
B
Vest4
0.43
MutPred
0.47
Loss of methylation at R39 (P = 0.0022);
MVP
0.10
MPC
1.4
ClinPred
0.17
T
GERP RS
4.9
RBP_binding_hub_radar
1.1
RBP_regulation_power_radar
2.9
Varity_R
0.19
gMVP
0.30

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1247455356; hg19: chr10-101379977; API