8-23566156-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016612.4(SLC25A37):​c.259A>G​(p.Ile87Val) variant causes a missense change. The variant allele was found at a frequency of 0.262 in 1,602,702 control chromosomes in the GnomAD database, including 57,752 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (4154 hom., cov: 33)
  • Exomes 𝑓: 0.27 (53598 hom.)
• Consequence: SLC25A37 NM_016612.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.54
• Publications: 53 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014241934).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A37	NM_016612.4	c.259A>G	p.Ile87Val	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>G	p.Ile87Val	missense_variant	Exon 2 of 4	1	NM_016612.4	ENSP00000429200.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31787 AN: 152078 Hom.: 4147 Cov.: 33

Gnomad AFR AF: 0.0539

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.236

GnomAD2 exomes AF: 0.250 AC: 59544 AN: 237848 AF XY: 0.253

Gnomad AFR exome AF: 0.0501

Gnomad AMR exome AF: 0.280

Gnomad ASJ exome AF: 0.252

Gnomad EAS exome AF: 0.203

Gnomad FIN exome AF: 0.268

Gnomad NFE exome AF: 0.286

Gnomad OTH exome AF: 0.256

GnomAD4 exome AF: 0.267 AC: 387874 AN: 1450506 Hom.: 53598 Cov.: 35 AF XY: 0.266 AC XY: 192225 AN XY: 721352

African (AFR) AF: 0.0446 AC: 1470 AN: 32946

American (AMR) AF: 0.277 AC: 11466 AN: 41468

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 6458 AN: 25900

East Asian (EAS) AF: 0.167 AC: 6564 AN: 39222

South Asian (SAS) AF: 0.211 AC: 17619 AN: 83596

European-Finnish (FIN) AF: 0.265 AC: 14134 AN: 53312

Middle Eastern (MID) AF: 0.266 AC: 1525 AN: 5736

European-Non Finnish (NFE) AF: 0.283 AC: 313451 AN: 1108346

Other (OTH) AF: 0.253 AC: 15187 AN: 59980

GnomAD4 genome AF: 0.209 AC: 31802 AN: 152196 Hom.: 4154 Cov.: 33 AF XY: 0.209 AC XY: 15582 AN XY: 74410

African (AFR) AF: 0.0538 AC: 2235 AN: 41558

American (AMR) AF: 0.262 AC: 4007 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 867 AN: 3466

East Asian (EAS) AF: 0.207 AC: 1070 AN: 5166

South Asian (SAS) AF: 0.200 AC: 966 AN: 4818

European-Finnish (FIN) AF: 0.257 AC: 2715 AN: 10582

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19060 AN: 67986

Other (OTH) AF: 0.240 AC: 508 AN: 2116

Alfa AF: 0.251 Hom.: 13708

Bravo AF: 0.206

TwinsUK AF: 0.266 AC: 988

ALSPAC AF: 0.283 AC: 1091

ESP6500AA AF: 0.0597 AC: 224

ESP6500EA AF: 0.276 AC: 2270

ExAC AF: 0.253 AC: 30561

Asia WGS AF: 0.200 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	9.4
DANN	Benign	0.59
DEOGEN2	Benign	0.064	T;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.78	T;T
MetaRNN	Benign	0.0014	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.50	N;.
PhyloP100		4.5
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.040	N;N
REVEL	Benign	0.24
Sift	Benign	0.94	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.031
MPC		0.32
ClinPred		0.0025	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.049
gMVP		0.35
Mutation Taster		=92/8	polymorphism (auto)

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; COSMIC: COSV51563543; COSMIC: COSV51563543;