8-23571836-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016612.4(SLC25A37):ā€‹c.998A>Gā€‹(p.Glu333Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,611,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000096 ( 0 hom. )

Consequence

SLC25A37
NM_016612.4 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.42
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13967094).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC25A37NM_016612.4 linkuse as main transcriptc.998A>G p.Glu333Gly missense_variant 4/4 ENST00000519973.6 NP_057696.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC25A37ENST00000519973.6 linkuse as main transcriptc.998A>G p.Glu333Gly missense_variant 4/41 NM_016612.4 ENSP00000429200 P1Q9NYZ2-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152206
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000162
AC:
4
AN:
246926
Hom.:
0
AF XY:
0.0000223
AC XY:
3
AN XY:
134536
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000359
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000959
AC:
14
AN:
1459262
Hom.:
0
Cov.:
32
AF XY:
0.00000827
AC XY:
6
AN XY:
725380
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:
0.0000126
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152206
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
ExAC
AF:
0.0000331
AC:
4
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsOct 13, 2023The c.998A>G (p.E333G) alteration is located in exon 4 (coding exon 4) of the SLC25A37 gene. This alteration results from a A to G substitution at nucleotide position 998, causing the glutamic acid (E) at amino acid position 333 to be replaced by a glycine (G). 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
Benign
0.11
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.26
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T
Eigen
Benign
0.12
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-0.37
T
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
0.80
D
PrimateAI
Benign
0.42
T
PROVEAN
Uncertain
-2.8
D
REVEL
Benign
0.27
Sift
Benign
0.049
D
Sift4G
Benign
0.15
T
Polyphen
0.0020
B
Vest4
0.27
MutPred
0.33
Gain of MoRF binding (P = 0.0215);
MVP
0.45
MPC
0.49
ClinPred
0.47
T
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.17
gMVP
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs759792762; hg19: chr8-23429349; API