rs11186926

chr10-92338564-G-C

Variant summary

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

The NM_017824.5(MARCHF5):c.239-2109G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,056 control chromosomes in the GnomAD database, including 10,745 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 0.34 (10745 hom., cov: 31)
• Consequence: MARCHF5 NM_017824.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MARCHF5	NM_017824.5	c.239-2109G>C		intron_variant		ENST00000358935.3
MARCHF5	XM_047425382.1	c.17-2109G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARCHF5	ENST00000358935.3	c.239-2109G>C		intron_variant		1	NM_017824.5	P1
MARCHF5	ENST00000462465.1	n.120-2109G>C		intron_variant, non_coding_transcript_variant		3
MARCHF5	ENST00000467521.6	n.330-2109G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51000 AN: 151938 Hom.: 10755 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.335 AC: 50977 AN: 152056 Hom.: 10745 Cov.: 31 AF XY: 0.328 AC XY: 24349 AN XY: 74330

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.408

Alfa AF: 0.395 Hom.: 1666

Bravo AF: 0.328

Asia WGS AF: 0.194 AC: 675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.7
Dann	Benign	0.75

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: rs11186926; hg19: chr10-94098321;