rs11781222

Positions:

• chr8-23532058-T-C

Variant summary

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

The NM_016612.4(SLC25A37):​c.210+2846T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,010 control chromosomes in the GnomAD database, including 1,243 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1243 hom., cov: 32)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: SLC25A37 NM_016612.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156

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]

SLC25A37 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A37	NM_016612.4	c.210+2846T>C		intron_variant		ENST00000519973.6	NP_057696.2
SLC25A37	NM_001317813.2	c.-131+2846T>C		intron_variant			NP_001304742.1
SLC25A37	NM_001317814.2	c.-78+2846T>C		intron_variant			NP_001304743.1
SLC25A37	NM_001317812.2	c.-721+2846T>C		intron_variant			NP_001304741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A37	ENST00000519973.6	c.210+2846T>C		intron_variant		1	NM_016612.4	ENSP00000429200.1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17650 AN: 151882 Hom.: 1239 Cov.: 32

Gnomad AFR AF: 0.0613

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0730

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.100 AC: 1 AN: 10 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.116 AC: 17680 AN: 152000 Hom.: 1243 Cov.: 32 AF XY: 0.117 AC XY: 8680 AN XY: 74314

Gnomad4 AFR AF: 0.0615

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.0730

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.146

Alfa AF: 0.129 Hom.: 787

Bravo AF: 0.118

Asia WGS AF: 0.227 AC: 790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.2
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs11781222; hg19: chr8-23389571;