Variant 8-23529203-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_016612.4(SLC25A37):c.201C>G(p.Asp67Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000687 in 1,455,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

SLC25A37
NM_016612.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.56

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.976

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC25A37	NM_016612.4 linkuse as main transcript	c.201C>G	p.Asp67Glu	missense_variant	1/4	ENST00000519973.6	NP_057696.2
SLC25A37	NM_001317812.2 linkuse as main transcript	c.-730C>G		5_prime_UTR_variant	1/4		NP_001304741.1
SLC25A37	NM_001317813.2 linkuse as main transcript	c.-140C>G		5_prime_UTR_variant	1/5		NP_001304742.1
SLC25A37	NM_001317814.2 linkuse as main transcript	c.-87C>G		5_prime_UTR_variant	1/5		NP_001304743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A37	ENST00000519973.6 linkuse as main transcript	c.201C>G	p.Asp67Glu	missense_variant	1/4	1	NM_016612.4	ENSP00000429200	P1	Q9NYZ2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000687

AC:

AN:

1455868

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724194

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000901

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

The c.201C>G (p.D67E) alteration is located in exon 1 (coding exon 1) of the SLC25A37 gene. This alteration results from a C to G substitution at nucleotide position 201, causing the aspartic acid (D) at amino acid position 67 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

T;.

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.68

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Pathogenic

0.62

MetaRNN

Pathogenic

0.98

D;D

MetaSVM

Uncertain

0.41

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.5

D;D

REVEL

Pathogenic

0.81

Sift

Uncertain

0.0030

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.91

MutPred

0.95

Gain of phosphorylation at Y64 (P = 0.0847);.;

MVP

0.96

MPC

1.1

ClinPred

0.98

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.62

gMVP

0.79

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over