10-99610992-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_031212.4(SLC25A28):​c.952G>A​(p.Val318Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,614,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

SLC25A28
NM_031212.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.36
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 -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09783375).
BS2
High AC in GnomAdExome4 at 30 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC25A28NM_031212.4 linkc.952G>A p.Val318Ile missense_variant Exon 4 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.952G>A p.Val318Ile missense_variant Exon 4 of 4 1 NM_031212.4 ENSP00000359526.4 Q96A46-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152214
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
249568
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135400
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000265
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000205
AC:
30
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.0000193
AC XY:
14
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000243
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152332
Hom.:
0
Cov.:
32
AF XY:
0.0000268
AC XY:
2
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.00000827
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 18, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.952G>A (p.V318I) alteration is located in exon 4 (coding exon 4) of the SLC25A28 gene. This alteration results from a G to A substitution at nucleotide position 952, causing the valine (V) at amino acid position 318 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Uncertain:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.095
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
22
DANN
Benign
0.96
DEOGEN2
Benign
0.15
.;T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.000022
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.80
T;T
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.098
T;T
MetaSVM
Benign
-0.79
T
MutationAssessor
Benign
0.39
.;N
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
0.29
N;N
REVEL
Uncertain
0.34
Sift
Benign
0.39
T;T
Sift4G
Benign
0.40
T;T
Polyphen
0.0090
.;B
Vest4
0.14
MutPred
0.30
.;Gain of MoRF binding (P = 0.1384);
MVP
0.30
MPC
0.99
ClinPred
0.11
T
GERP RS
5.3
Varity_R
0.083
gMVP
0.57

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: rs766776544; hg19: chr10-101370749; API