chr8-23566156-A-T

Variant names:

• chr8-23566156-A-T
• rs2942194
• NM_016612.4:c.259A>T

Variant summary

Our verdict is Uncertain significance. The variant received 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.

• 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A37	NM_016612.4	MANE Select	c.259A>T	p.Ile87Phe	missense	Exon 2 of 4	NP_057696.2	Q9NYZ2-1
	SLC25A37	NM_001317813.2		c.43A>T	p.Ile15Phe	missense	Exon 3 of 5	NP_001304742.1
	SLC25A37	NM_001317814.2		c.43A>T	p.Ile15Phe	missense	Exon 3 of 5	NP_001304743.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A37	ENST00000519973.6	TSL:1 MANE Select	c.259A>T	p.Ile87Phe	missense	Exon 2 of 4	ENSP00000429200.1	Q9NYZ2-1
	SLC25A37	ENST00000290075.10	TSL:1	n.259A>T		non_coding_transcript_exon	Exon 2 of 4	ENSP00000290075.6	Q9NYZ2-2
	SLC25A37	ENST00000518881.5	TSL:1	n.295A>T		non_coding_transcript_exon	Exon 2 of 3

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

African (AFR) AF: 0.00 AC: 0 AN: 32958

American (AMR) AF: 0.00 AC: 0 AN: 41642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25918

East Asian (EAS) AF: 0.00 AC: 0 AN: 39246

South Asian (SAS) AF: 0.00 AC: 0 AN: 83718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108628

Other (OTH) AF: 0.0000167 AC: 1 AN: 59998

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.5
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.0080	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
Mutation Taster		=62/38	polymorphism

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

Other links and lift over

dbSNP: rs2942194; hg19: chr8-23423669;