rs11186914

chr10-92302874-T-Achr10-92302874-T-C

Variant summary

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

The NM_017824.5(MARCHF5):c.36-8261T>A 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 152,064 control chromosomes in the GnomAD database, including 23,434 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 (23434 hom., cov: 32)
• Consequence: MARCHF5 NM_017824.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MARCHF5	NM_017824.5	c.36-8261T>A		intron_variant		ENST00000358935.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARCHF5	ENST00000358935.3	c.36-8261T>A		intron_variant		1	NM_017824.5	P1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83430 AN: 151946 Hom.: 23437 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.549 AC: 83462 AN: 152064 Hom.: 23434 Cov.: 32 AF XY: 0.542 AC XY: 40266 AN XY: 74328

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.615

Alfa AF: 0.560 Hom.: 2976

Bravo AF: 0.566

Asia WGS AF: 0.465 AC: 1621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	13
Dann	Benign	0.85

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: rs11186914; hg19: chr10-94062631;