rs11186926

Variant names:

• chr10-92338564-G-C
• rs11186926
• NM_017824.5:c.239-2109G>C

Variant summary

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

The NM_017824.5(MARCHF5):​c.239-2109G>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
• Publications: 2 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=-0.89).
• 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 rank	MANE	Protein	UniProt
MARCHF5	NM_017824.5	c.239-2109G>C		intron_variant	Intron 2 of 5	ENST00000358935.3	NP_060294.1
MARCHF5	XM_047425382.1	c.17-2109G>C		intron_variant	Intron 2 of 5		XP_047281338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCHF5	ENST00000358935.3	c.239-2109G>C		intron_variant	Intron 2 of 5	1	NM_017824.5	ENSP00000351813.2
MARCHF5	ENST00000462465.1	n.120-2109G>C		intron_variant	Intron 1 of 2	3
MARCHF5	ENST00000467521.6	n.330-2109G>C		intron_variant	Intron 2 of 4	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

African (AFR) AF: 0.109 AC: 4519 AN: 41494

American (AMR) AF: 0.356 AC: 5443 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1921 AN: 3470

East Asian (EAS) AF: 0.130 AC: 672 AN: 5178

South Asian (SAS) AF: 0.244 AC: 1177 AN: 4820

European-Finnish (FIN) AF: 0.363 AC: 3830 AN: 10548

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32132 AN: 67958

Other (OTH) AF: 0.408 AC: 863 AN: 2116

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
PhyloP100		-1.5
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: rs11186926; hg19: chr10-94098321;