10-99620215-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_031212.4(SLC25A28):​c.121G>A​(p.Ala41Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000488 in 1,394,038 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A41G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

SLC25A28
NM_031212.4 missense

Scores

2
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.02502808).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC25A28NM_031212.4 linkc.121G>A p.Ala41Thr 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.121G>A p.Ala41Thr missense_variant Exon 1 of 4 1 NM_031212.4 ENSP00000359526.4 Q96A46-1

Frequencies

GnomAD3 genomes
AF:
0.0000334
AC:
5
AN:
149748
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000245
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000844
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000412
AC:
14
AN:
34016
Hom.:
0
AF XY:
0.000403
AC XY:
8
AN XY:
19840
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00154
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00106
GnomAD4 exome
AF:
0.0000506
AC:
63
AN:
1244192
Hom.:
0
Cov.:
34
AF XY:
0.0000707
AC XY:
43
AN XY:
608548
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000902
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000988
GnomAD4 genome
AF:
0.0000334
AC:
5
AN:
149846
Hom.:
0
Cov.:
32
AF XY:
0.0000410
AC XY:
3
AN XY:
73114
show subpopulations
Gnomad4 AFR
AF:
0.0000245
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000845
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.000125
AC:
8

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 05, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.121G>A (p.A41T) alteration is located in exon 1 (coding exon 1) of the SLC25A28 gene. This alteration results from a G to A substitution at nucleotide position 121, causing the alanine (A) at amino acid position 41 to be replaced by a threonine (T). 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
0.089
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.077
T
Eigen
Benign
-0.40
Eigen_PC
Benign
-0.20
FATHMM_MKL
Benign
0.41
N
LIST_S2
Benign
0.58
T
M_CAP
Pathogenic
0.97
D
MetaRNN
Benign
0.025
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.34
N
PrimateAI
Pathogenic
0.94
D
PROVEAN
Benign
0.020
N
REVEL
Benign
0.17
Sift
Benign
0.087
T
Sift4G
Benign
0.36
T
Polyphen
0.0
B
Vest4
0.21
MutPred
0.37
Gain of phosphorylation at A41 (P = 0.0124);
MVP
0.15
MPC
1.1
ClinPred
0.067
T
GERP RS
4.0
RBP_binding_hub_radar
1.1
RBP_regulation_power_radar
2.9
Varity_R
0.12
gMVP
0.34

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: rs538605958; hg19: chr10-101379972; API