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

Variant summary

Our verdict is Likely benign. The variant received -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. 14/22 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

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: Likely_benign. The variant received -6 ACMG points.

BP4

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

BS2

High AC in GnomAdExome4 at 9 AD gene.

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.41G>A	p.Gly14Glu	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.41G>A	p.Gly14Glu	missense	Exon 1 of 4	ENSP00000359526.4	Q96A46-1
SLC25A28	ENST00000913498.1		c.41G>A	p.Gly14Glu	missense	Exon 1 of 4	ENSP00000583557.1
SLC25A28	ENST00000966520.1		c.41G>A	p.Gly14Glu	missense	Exon 1 of 3	ENSP00000636579.1

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

African (AFR)

AF:

0.00

AC:

AN:

20674

American (AMR)

AF:

0.00

AC:

AN:

7250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11790

East Asian (EAS)

AF:

0.00

AC:

AN:

20838

South Asian (SAS)

AF:

0.00

AC:

AN:

20038

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18902

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2648

European-Non Finnish (NFE)

AF:

0.00000792

AC:

AN:

883916

Other (OTH)

AF:

0.0000507

AC:

AN:

39470

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000672

AC:

AN:

148878

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72602

show subpopulations

African (AFR)

AF:

0.0000246

AC:

AN:

40660

American (AMR)

AF:

0.00

AC:

AN:

15024

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3440

East Asian (EAS)

AF:

0.00

AC:

AN:

5040

South Asian (SAS)

AF:

0.00

AC:

AN:

4754

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9858

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66844

Other (OTH)

AF:

0.00

AC:

AN:

2046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

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

0.12

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

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

PhyloP100

1.2

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

PromoterAI

-0.036

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

4.0

Varity_R

0.28

gMVP

0.62

Mutation Taster

=90/10

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over