8-23529203-C-G

Variant names:

• chr8-23529203-C-G
• rs1801609564
• NM_016612.4:c.201C>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.56
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.976

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.201C>G	p.Asp67Glu	missense	Exon 1 of 4	NP_057696.2	Q9NYZ2-1
	SLC25A37	NM_001317813.2		c.-140C>G		5_prime_UTR	Exon 1 of 5	NP_001304742.1
	SLC25A37	NM_001317814.2		c.-87C>G		5_prime_UTR	Exon 1 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.201C>G	p.Asp67Glu	missense	Exon 1 of 4	ENSP00000429200.1	Q9NYZ2-1
	SLC25A37	ENST00000290075.10	TSL:1	n.201C>G		non_coding_transcript_exon	Exon 1 of 4	ENSP00000290075.6	Q9NYZ2-2
	SLC25A37	ENST00000518881.5	TSL:1	n.237C>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000687 AC: 10 AN: 1455868 Hom.: 0 Cov.: 31 AF XY: 0.00000552 AC XY: 4 AN XY: 724194

African (AFR) AF: 0.00 AC: 0 AN: 32692

American (AMR) AF: 0.00 AC: 0 AN: 44264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25936

East Asian (EAS) AF: 0.00 AC: 0 AN: 39064

South Asian (SAS) AF: 0.00 AC: 0 AN: 85422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52730

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000901 AC: 10 AN: 1109866

Other (OTH) AF: 0.00 AC: 0 AN: 60148

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.68	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Pathogenic	0.62	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.41	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.6
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.5	D
REVEL	Pathogenic	0.81
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	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	D
GERP RS		3.2
PromoterAI		-0.052	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.62
gMVP		0.79
Mutation Taster		=64/36	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: rs1801609564; hg19: chr8-23386716;