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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A28	NM_031212.4 link	c.521-55A>G		intron_variant	Intron 2 of 3	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.521-55A>G		intron_variant	Intron 2 of 3	1	NM_031212.4	ENSP00000359526.4		Q96A46-1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over