8-23540402-T-C

Variant names:

• chr8-23540402-T-C
• rs12548753
• NM_016612.4:c.210+11190T>C

Variant summary

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

The NM_016612.4(SLC25A37):​c.210+11190T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,024 control chromosomes in the GnomAD database, including 12,417 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 0.38 (12417 hom., cov: 32)
• Consequence: SLC25A37 NM_016612.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.744
• Publications: 5 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 (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A37	NM_016612.4	MANE Select	c.210+11190T>C		intron	N/A	NP_057696.2
	SLC25A37	NM_001317813.2		c.-130-2686T>C		intron	N/A	NP_001304742.1
	SLC25A37	NM_001317814.2		c.-7+3498T>C		intron	N/A	NP_001304743.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A37	ENST00000519973.6	TSL:1 MANE Select	c.210+11190T>C		intron	N/A	ENSP00000429200.1
	SLC25A37	ENST00000290075.10	TSL:1	n.210+11190T>C		intron	N/A	ENSP00000290075.6
	SLC25A37	ENST00000518881.5	TSL:1	n.246+11190T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56979 AN: 151904 Hom.: 12376 Cov.: 32

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.355

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.375 AC: 57075 AN: 152024 Hom.: 12417 Cov.: 32 AF XY: 0.380 AC XY: 28197 AN XY: 74292

African (AFR) AF: 0.569 AC: 23562 AN: 41434

American (AMR) AF: 0.435 AC: 6655 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 893 AN: 3468

East Asian (EAS) AF: 0.615 AC: 3168 AN: 5152

South Asian (SAS) AF: 0.422 AC: 2030 AN: 4814

European-Finnish (FIN) AF: 0.266 AC: 2811 AN: 10576

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16898 AN: 67984

Other (OTH) AF: 0.356 AC: 750 AN: 2108

Alfa AF: 0.320 Hom.: 1386

Bravo AF: 0.393

Asia WGS AF: 0.502 AC: 1745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.60
DANN	Benign	0.50
PhyloP100		-0.74
Mutation Taster		=100/0	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: rs12548753; hg19: chr8-23397915;