Genetic Variant SLC25A28:p.Ala27Thr (chr10-99620257-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031212.4(SLC25A28):c.79G>A(p.Ala27Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. A27V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 26)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC25A28
NM_031212.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15

Publications

0 publications found

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:

ENSG00000229278 (HGNC:):

ENSG00000229278 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18287754).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031212.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A28	NM_031212.4	MANE Select	c.79G>A	p.Ala27Thr	missense	Exon 1 of 4	NP_112489.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC25A28	ENST00000370495.6	TSL:1 MANE Select	c.79G>A	p.Ala27Thr	missense	Exon 1 of 4	ENSP00000359526.4	Q96A46-1
SLC25A28	ENST00000913498.1		c.79G>A	p.Ala27Thr	missense	Exon 1 of 4	ENSP00000583557.1
SLC25A28	ENST00000966520.1		c.79G>A	p.Ala27Thr	missense	Exon 1 of 3	ENSP00000636579.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1133922

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

548078

African (AFR)

AF:

0.00

AC:

AN:

22932

American (AMR)

AF:

0.00

AC:

AN:

9150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14936

East Asian (EAS)

AF:

0.00

AC:

AN:

26486

South Asian (SAS)

AF:

0.00

AC:

AN:

38444

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24036

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3016

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

949710

Other (OTH)

AF:

0.00

AC:

AN:

45212

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.087

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.50

M_CAP

Pathogenic

0.92

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.34

PhyloP100

2.1

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.10

REVEL

Benign

0.14

Sift

Benign

0.12

Sift4G

Benign

0.64

Polyphen

0.0

Vest4

0.11

MutPred

0.33

Loss of helix (P = 0.0167)

MVP

0.20

MPC

1.1

ClinPred

0.28

GERP RS

3.8

PromoterAI

-0.00030

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.3

Varity_R

0.10

gMVP

0.48

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over