dbSNP rs538605958: SLC25A28:p.Ala41Thr (chr10-99620215-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -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. 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. 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

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02502808).

BS2

High AC in GnomAd4 at 5 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.121G>A	p.Ala41Thr	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.121G>A	p.Ala41Thr	missense	Exon 1 of 4	ENSP00000359526.4	Q96A46-1
SLC25A28	ENST00000913498.1		c.121G>A	p.Ala41Thr	missense	Exon 1 of 4	ENSP00000583557.1
SLC25A28	ENST00000966520.1		c.121G>A	p.Ala41Thr	missense	Exon 1 of 3	ENSP00000636579.1

Frequencies

GnomAD3 genomes

AF:

0.0000334

AC:

AN:

149748

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000412

AC:

AN:

34016

AF XY:

0.000403

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00106

GnomAD4 exome

AF:

0.0000506

AC:

AN:

1244192

Hom.:

Cov.:

AF XY:

0.0000707

AC XY:

AN XY:

608548

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25126

American (AMR)

AF:

0.00

AC:

AN:

18924

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18816

East Asian (EAS)

AF:

0.00

AC:

AN:

27804

South Asian (SAS)

AF:

0.000902

AC:

AN:

63194

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29732

Middle Eastern (MID)

AF:

0.000284

AC:

AN:

3526

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1006484

Other (OTH)

AF:

0.0000988

AC:

AN:

50586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.552

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:

0.0000334

AC:

AN:

149846

Hom.:

Cov.:

AF XY:

0.0000410

AC XY:

AN XY:

73114

show subpopulations

African (AFR)

AF:

0.0000245

AC:

AN:

40870

American (AMR)

AF:

0.00

AC:

AN:

15132

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3440

East Asian (EAS)

AF:

0.00

AC:

AN:

5026

South Asian (SAS)

AF:

0.000845

AC:

AN:

4732

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10198

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67184

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.000125

AC:

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

0.089

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.077

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.58

M_CAP

Pathogenic

0.97

MetaRNN

Benign

0.025

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.34

PhyloP100

2.1

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

0.020

REVEL

Benign

0.17

Sift

Benign

0.087

Sift4G

Benign

0.36

Polyphen

0.0

Vest4

0.21

MutPred

0.37

Gain of phosphorylation at A41 (P = 0.0124)

MVP

0.15

MPC

1.1

ClinPred

0.067

GERP RS

4.0

PromoterAI

0.024

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.9

Varity_R

0.12

gMVP

0.34

Mutation Taster

=88/12

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over