Genetic Variant SLC25A37:c.440-154C>T (chr8-23568168-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_016612.4(SLC25A37):c.440-154C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 773,384 control chromosomes in the GnomAD database, including 222 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 0.018 ( 69 hom., cov: 31)

Exomes 𝑓: 0.0081 ( 153 hom. )

Consequence

SLC25A37
NM_016612.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.51

Publications

2 publications found

Variant links:

Genes affected

SLC25A37 (HGNC:29786): (solute carrier family 25 member 37) SLC25A37 is a solute carrier localized in the mitochondrial inner membrane. It functions as an essential iron importer for the synthesis of mitochondrial heme and iron-sulfur clusters (summary by Chen et al., 2009 [PubMed 19805291]).[supplied by OMIM, Jan 2011]

SLC25A37 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0612 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016612.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC25A37	NM_016612.4	MANE Select	c.440-154C>T	intron	N/A	NP_057696.2
SLC25A37	NM_001317813.2		c.224-154C>T	intron	N/A	NP_001304742.1
SLC25A37	NM_001317814.2		c.224-154C>T	intron	N/A	NP_001304743.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC25A37	ENST00000519973.6	TSL:1 MANE Select	c.440-154C>T	intron	N/A	ENSP00000429200.1
SLC25A37	ENST00000518881.5	TSL:1	n.2307C>T	non_coding_transcript_exon	Exon 2 of 3
SLC25A37	ENST00000520654.1	TSL:1	n.2221C>T	non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0179

AC:

2717

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0510

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00779

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0671

Gnomad SAS

AF:

0.0149

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0196

GnomAD4 exome

AF:

0.00813

AC:

5052

AN:

621132

Hom.:

153

Cov.:

AF XY:

0.00792

AC XY:

2658

AN XY:

335754

show subpopulations

African (AFR)

AF:

0.0525

AC:

916

AN:

17434

American (AMR)

AF:

0.00461

AC:

179

AN:

38830

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20524

East Asian (EAS)

AF:

0.0762

AC:

2664

AN:

34940

South Asian (SAS)

AF:

0.0128

AC:

861

AN:

67528

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49292

Middle Eastern (MID)

AF:

0.00631

AC:

AN:

4122

European-Non Finnish (NFE)

AF:

0.000416

AC:

148

AN:

355614

Other (OTH)

AF:

0.00785

AC:

258

AN:

32848

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

239

478

718

957

1196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.0180

AC:

2738

AN:

152252

Hom.:

Cov.:

AF XY:

0.0184

AC XY:

1369

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0513

AC:

2131

AN:

41528

American (AMR)

AF:

0.00778

AC:

119

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0670

AC:

347

AN:

5178

South Asian (SAS)

AF:

0.0145

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000353

AC:

AN:

68016

Other (OTH)

AF:

0.0218

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

129

258

387

516

645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0106

Hom.:

Bravo

AF:

0.0199

Asia WGS

AF:

0.0490

AC:

172

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.064

(source)

DANN

Benign

0.48

PhyloP100

-2.5

Mutation Taster

=100/0

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

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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