Genetic Variant SLC25A28:p.Gly14Glu (chr10-99620295-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

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

The NM_031212.4(SLC25A28):c.41G>A(p.Gly14Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000851 in 1,174,404 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 0.0000067 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0000088 ( 0 hom. )

Consequence

SLC25A28
NM_031212.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.24

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]

SLC25A28 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20730558).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A28	NM_031212.4 link	c.41G>A	p.Gly14Glu	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
SLC25A28	ENST00000370495.6 link	c.41G>A	p.Gly14Glu	missense_variant	Exon 1 of 4	1	NM_031212.4	ENSP00000359526.4		Q96A46-1

Frequencies

GnomAD3 genomes

AF:

0.00000672

AC:

AN:

148878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000878

AC:

AN:

1025526

Hom.:

Cov.:

AF XY:

0.00000616

AC XY:

AN XY:

487012

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000792

Gnomad4 OTH exome

AF:

0.0000507

GnomAD4 genome

AF:

0.00000672

AC:

AN:

148878

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72602

show subpopulations

Gnomad4 AFR

AF:

0.0000246

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.41G>A (p.G14E) 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 41, causing the glycine (G) at amino acid position 14 to be replaced by a glutamic acid (E). 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

0.12

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.082

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.52

M_CAP

Pathogenic

0.97

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.34

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.11

REVEL

Benign

0.16

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.012

Polyphen

0.0

Vest4

0.20

MutPred

0.34

Gain of solvent accessibility (P = 0.0638);

MVP

0.068

MPC

1.5

ClinPred

0.54

GERP RS

4.0

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

4.0

Varity_R

0.28

gMVP

0.62

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over