rs3736032

Positions:

• chr8-23566184-G-A
• chr8-23566184-G-C
• chr8-23566184-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016612.4(SLC25A37):​c.287G>A​(p.Arg96Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.082 in 1,605,314 control chromosomes in the GnomAD database, including 6,617 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.11 (1287 hom., cov: 33)
  • Exomes 𝑓: 0.079 (5330 hom.)
• Consequence: SLC25A37 NM_016612.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

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=0.0014380515).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A37	NM_016612.4	c.287G>A	p.Arg96Gln	missense_variant	2/4	ENST00000519973.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A37	ENST00000519973.6	c.287G>A	p.Arg96Gln	missense_variant	2/4	1	NM_016612.4	P1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17163 AN: 152066 Hom.: 1283 Cov.: 33

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0630

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0803

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0690

Gnomad OTH AF: 0.0947

GnomAD3 exomes AF: 0.0889 AC: 21377 AN: 240552 Hom.: 1235 AF XY: 0.0886 AC XY: 11600 AN XY: 130852

Gnomad AFR exome AF: 0.212

Gnomad AMR exome AF: 0.0348

Gnomad ASJ exome AF: 0.0996

Gnomad EAS exome AF: 0.147

Gnomad SAS exome AF: 0.129

Gnomad FIN exome AF: 0.0759

Gnomad NFE exome AF: 0.0700

Gnomad OTH exome AF: 0.0780

GnomAD4 exome AF: 0.0787 AC: 114427 AN: 1453130 Hom.: 5330 Cov.: 51 AF XY: 0.0794 AC XY: 57361 AN XY: 722732

Gnomad4 AFR exome AF: 0.213

Gnomad4 AMR exome AF: 0.0386

Gnomad4 ASJ exome AF: 0.0993

Gnomad4 EAS exome AF: 0.164

Gnomad4 SAS exome AF: 0.124

Gnomad4 FIN exome AF: 0.0738

Gnomad4 NFE exome AF: 0.0690

Gnomad4 OTH exome AF: 0.0903

GnomAD4 genome AF: 0.113 AC: 17178 AN: 152184 Hom.: 1287 Cov.: 33 AF XY: 0.111 AC XY: 8269 AN XY: 74416

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.0629

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0803

Gnomad4 NFE AF: 0.0690

Gnomad4 OTH AF: 0.0966

Alfa AF: 0.0806 Hom.: 1062

Bravo AF: 0.115

TwinsUK AF: 0.0717 AC: 266

ALSPAC AF: 0.0646 AC: 249

ESP6500AA AF: 0.210 AC: 794

ESP6500EA AF: 0.0694 AC: 571

ExAC AF: 0.0937 AC: 11318

Asia WGS AF: 0.159 AC: 551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.28	N
LIST_S2	Uncertain	0.90	D;D
MetaRNN	Benign	0.0014	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.
MutationTaster	Benign	0.18	P
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.12
Sift	Benign	0.17	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.055	B;.
Vest4		0.061
MPC		0.45
ClinPred		0.0028	T
GERP RS		0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.081
gMVP		0.51

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: rs3736032; hg19: chr8-23423697;