8-23566156-A-T

Variant names:

• chr8-23566156-A-T
• NM_016612.4:c.259A>T

Variant summary

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

The NM_016612.4(SLC25A37):​c.259A>T​(p.Ile87Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,451,168 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. I87V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC25A37 NM_016612.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.54

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 rank	MANE	Protein	UniProt
SLC25A37	NM_016612.4	c.259A>T	p.Ile87Phe	missense_variant	Exon 2 of 4	ENST00000519973.6	NP_057696.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A37	ENST00000519973.6	c.259A>T	p.Ile87Phe	missense_variant	Exon 2 of 4	1	NM_016612.4	ENSP00000429200.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451168 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 721692

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: 0.00

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.42	T;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.026	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.0060	B;.
Vest4		0.48
MutPred		0.63		Loss of catalytic residue at I87 (P = 0.0076);.;
MVP		0.66
MPC		0.65
ClinPred		0.96	D
GERP RS		3.5
Varity_R		0.42
gMVP		0.86

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.

Other links and lift over

hg19: chr8-23423669;