10-92330741-A-G

Variant names:

• chr10-92330741-A-G
• rs10748579
• NM_017824.5:c.239-9932A>G

Variant summary

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

The NM_017824.5(MARCHF5):​c.239-9932A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,082 control chromosomes in the GnomAD database, including 23,432 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 0.55 (23432 hom., cov: 32)
• Consequence: MARCHF5 NM_017824.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• Publications: 8 publications found

Genes affected

MARCHF5 (HGNC:26025): (membrane associated ring-CH-type finger 5) MARCH5 is a ubiquitin ligase of the mitochondrial outer membrane that plays a role in the control of mitochondrial morphology by regulating mitofusin-2 (MFN2; MIM 608507) and DRP1 (DNM1L; MIM 603850) (Nakamura et al., 2006 [PubMed 16936636]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017824.5. 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
	MARCHF5	NM_017824.5	MANE Select	c.239-9932A>G		intron	N/A	NP_060294.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF5	ENST00000358935.3	TSL:1 MANE Select	c.239-9932A>G		intron	N/A	ENSP00000351813.2
	MARCHF5	ENST00000467521.6	TSL:3	n.330-9932A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83438 AN: 151964 Hom.: 23435 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.549 AC: 83468 AN: 152082 Hom.: 23432 Cov.: 32 AF XY: 0.542 AC XY: 40288 AN XY: 74354

African (AFR) AF: 0.457 AC: 18954 AN: 41474

American (AMR) AF: 0.662 AC: 10112 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2290 AN: 3466

East Asian (EAS) AF: 0.515 AC: 2670 AN: 5180

South Asian (SAS) AF: 0.432 AC: 2083 AN: 4822

European-Finnish (FIN) AF: 0.469 AC: 4953 AN: 10562

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40470 AN: 67980

Other (OTH) AF: 0.614 AC: 1299 AN: 2114

Alfa AF: 0.591 Hom.: 71963

Bravo AF: 0.566

Asia WGS AF: 0.466 AC: 1622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.48
PhyloP100		0.039
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: rs10748579; hg19: chr10-94090498;