10-92349730-T-A

Variant names:

• chr10-92349730-T-A
• NM_017824.5:c.613T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017824.5(MARCHF5):​c.613T>A​(p.Ser205Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MARCHF5 NM_017824.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF5	NM_017824.5	MANE Select	c.613T>A	p.Ser205Thr	missense	Exon 5 of 6	NP_060294.1	Q9NX47

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF5	ENST00000358935.3	TSL:1 MANE Select	c.613T>A	p.Ser205Thr	missense	Exon 5 of 6	ENSP00000351813.2	Q9NX47
	MARCHF5	ENST00000884892.1		c.610T>A	p.Ser204Thr	missense	Exon 5 of 6	ENSP00000554951.1
	MARCHF5	ENST00000919474.1		c.607T>A	p.Ser203Thr	missense	Exon 5 of 6	ENSP00000589533.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.8
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.21
Sift	Uncertain	0.023	D
Sift4G	Benign	0.096	T
Polyphen		0.90	P
Vest4		0.67
MutPred		0.54		Gain of relative solvent accessibility (P = 0.09)
MVP		0.67
MPC		0.95
ClinPred		0.90	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.42
gMVP		0.91
Mutation Taster		=48/52	disease causing

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

hg19: chr10-94109487;