Genetic Variant SLC25A28:c.521-55A>G (chr10-99612654-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_031212.4(SLC25A28):c.521-55A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 1,607,234 control chromosomes in the GnomAD database, including 608,909 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.85 ( 54808 hom., cov: 30)

Exomes 𝑓: 0.87 ( 554101 hom. )

Consequence

SLC25A28
NM_031212.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.398

Publications

11 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A28	NM_031212.4	MANE Select	c.521-55A>G		intron	N/A	NP_112489.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC25A28	ENST00000370495.6	TSL:1 MANE Select	c.521-55A>G	intron	N/A	ENSP00000359526.4
SLC25A28	ENST00000700252.1		n.1516A>G	non_coding_transcript_exon	Exon 2 of 3
SLC25A28	ENST00000700253.1		n.1583A>G	non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.848

AC:

128785

AN:

151938

Hom.:

54766

Cov.:

show subpopulations

Gnomad AFR

AF:

0.783

Gnomad AMI

AF:

0.814

Gnomad AMR

AF:

0.873

Gnomad ASJ

AF:

0.830

Gnomad EAS

AF:

0.787

Gnomad SAS

AF:

0.874

Gnomad FIN

AF:

0.889

Gnomad MID

AF:

0.924

Gnomad NFE

AF:

0.878

Gnomad OTH

AF:

0.856

GnomAD2 exomes

AF:

0.866

AC:

215238

AN:

248402

AF XY:

0.870

show subpopulations

Gnomad AFR exome

AF:

0.781

Gnomad AMR exome

AF:

0.901

Gnomad ASJ exome

AF:

0.837

Gnomad EAS exome

AF:

0.778

Gnomad FIN exome

AF:

0.889

Gnomad NFE exome

AF:

0.877

Gnomad OTH exome

AF:

0.873

GnomAD4 exome

AF:

0.872

AC:

1269072

AN:

1455178

Hom.:

554101

Cov.:

AF XY:

0.873

AC XY:

632344

AN XY:

724448

show subpopulations

African (AFR)

AF:

0.781

AC:

26040

AN:

33354

American (AMR)

AF:

0.899

AC:

40219

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.834

AC:

21742

AN:

26078

East Asian (EAS)

AF:

0.790

AC:

31315

AN:

39664

South Asian (SAS)

AF:

0.882

AC:

75922

AN:

86110

European-Finnish (FIN)

AF:

0.888

AC:

47247

AN:

53230

Middle Eastern (MID)

AF:

0.912

AC:

5177

AN:

5678

European-Non Finnish (NFE)

AF:

0.876

AC:

969361

AN:

1106158

Other (OTH)

AF:

0.865

AC:

52049

AN:

60192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

8402

16805

25207

33610

42012

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21158

42316

63474

84632

105790

<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:

0.848

AC:

128884

AN:

152056

Hom.:

54808

Cov.:

AF XY:

0.848

AC XY:

63033

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.783

AC:

32435

AN:

41432

American (AMR)

AF:

0.874

AC:

13355

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.830

AC:

2883

AN:

3472

East Asian (EAS)

AF:

0.787

AC:

4062

AN:

5160

South Asian (SAS)

AF:

0.874

AC:

4208

AN:

4812

European-Finnish (FIN)

AF:

0.889

AC:

9424

AN:

10596

Middle Eastern (MID)

AF:

0.921

AC:

269

AN:

292

European-Non Finnish (NFE)

AF:

0.878

AC:

59706

AN:

67990

Other (OTH)

AF:

0.855

AC:

1800

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

998

1995

2993

3990

4988

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<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:

0.867

Hom.:

183463

Bravo

AF:

0.843

Asia WGS

AF:

0.823

AC:

2866

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.1

(source)

DANN

Benign

0.52

PhyloP100

-0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

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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