8-23566184-G-C

Position:

• chr8-23566184-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016612.4(SLC25A37):​c.287G>C​(p.Arg96Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R96Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC25A37 NM_016612.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A37	NM_016612.4	c.287G>C	p.Arg96Pro	missense_variant	2/4	ENST00000519973.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A37	ENST00000519973.6	c.287G>C	p.Arg96Pro	missense_variant	2/4	1	NM_016612.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	D;.
Eigen	Benign	0.075
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.38	N
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Uncertain	0.19	D
MutationAssessor	Pathogenic	3.7	H;.
MutationTaster	Benign	0.027	P
PrimateAI	Benign	0.20	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Uncertain	0.58
Sift	Uncertain	0.017	D;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.93	P;.
Vest4		0.67
MutPred		0.45		Loss of MoRF binding (P = 0.0054);.;
MVP		0.92
MPC		1.3
ClinPred		0.99	D
GERP RS		0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.94
gMVP		0.94

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

LitVar

Other links and lift over

dbSNP: rs3736032; hg19: chr8-23423697;