Genetic Variant NM_016612.4:c.210+2846T>C (chr8-23532058-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_016612.4(SLC25A37):c.210+2846T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,010 control chromosomes in the GnomAD database, including 1,243 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 0.12 ( 1243 hom., cov: 32)

Exomes 𝑓: 0.10 ( 0 hom. )

Consequence

SLC25A37
NM_016612.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.156

Publications

16 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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 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	UniProt
SLC25A37	NM_016612.4	MANE Select	c.210+2846T>C	intron	N/A	NP_057696.2	Q9NYZ2-1
SLC25A37	NM_001317813.2		c.-131+2846T>C	intron	N/A	NP_001304742.1
SLC25A37	NM_001317814.2		c.-78+2846T>C	intron	N/A	NP_001304743.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC25A37	ENST00000519973.6	TSL:1 MANE Select	c.210+2846T>C	intron	N/A	ENSP00000429200.1	Q9NYZ2-1
SLC25A37	ENST00000290075.10	TSL:1	n.210+2846T>C	intron	N/A	ENSP00000290075.6	Q9NYZ2-2
SLC25A37	ENST00000518881.5	TSL:1	n.246+2846T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17650

AN:

151882

Hom.:

1239

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0613

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.0730

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.143

GnomAD4 exome

AF:

0.100

AC:

AN:

Hom.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.116

AC:

17680

AN:

152000

Hom.:

1243

Cov.:

AF XY:

0.117

AC XY:

8680

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.0615

AC:

2548

AN:

41446

American (AMR)

AF:

0.130

AC:

1980

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.146

AC:

505

AN:

3470

East Asian (EAS)

AF:

0.278

AC:

1439

AN:

5168

South Asian (SAS)

AF:

0.157

AC:

756

AN:

4822

European-Finnish (FIN)

AF:

0.0730

AC:

771

AN:

10566

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.135

AC:

9170

AN:

67968

Other (OTH)

AF:

0.146

AC:

308

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

801

1601

2402

3202

4003

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

220

440

660

880

1100

<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:

0.130

Hom.:

1122

Bravo

AF:

0.118

Asia WGS

AF:

0.227

AC:

790

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.2

(source)

DANN

Benign

0.53

PhyloP100

-0.16

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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