NM_016612.4:c.259A>G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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 Benign. Variant got -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

GnomAD3 exomes AF: 0.250 AC: 59544 AN: 237848 Hom.: 8080 AF XY: 0.253 AC XY: 32686 AN XY: 129320

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 SAS exome AF: 0.201

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

Gnomad4 AFR exome AF: 0.0446

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.249

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.283

Gnomad4 OTH exome AF: 0.253

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

Gnomad4 AFR AF: 0.0538

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.240

Alfa AF: 0.260 Hom.: 9896

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;.
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

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: rs2942194; hg19: chr8-23423669; COSMIC: COSV51563543; COSMIC: COSV51563543;