NM_178450.5:c.22C>A

Variant names:

• chr5-126918150-G-T
• NM_178450.5:c.22C>A

Variant summary

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

The NM_178450.5(MARCHF3):​c.22C>A​(p.His8Asn) variant causes a missense change. 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: MARCHF3 NM_178450.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.55
• Publications: 0 publications found

Genes affected

MARCHF3 (HGNC:28728): (membrane associated ring-CH-type finger 3) This gene encodes a member of the membrane-associated RING-CH (MARCH) family. The encoded protein is an E3 ubiquitin-protein ligase that may be involved in regulation of the endosomal transport pathway. [provided by RefSeq, Mar 2013]

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_178450.5. 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
	MARCHF3	NM_178450.5	MANE Select	c.22C>A	p.His8Asn	missense	Exon 2 of 5	NP_848545.1	Q86UD3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF3	ENST00000308660.6	TSL:1 MANE Select	c.22C>A	p.His8Asn	missense	Exon 2 of 5	ENSP00000309141.5	Q86UD3-1
	MARCHF3	ENST00000928511.1		c.22C>A	p.His8Asn	missense	Exon 2 of 6	ENSP00000598570.1
	MARCHF3	ENST00000968913.1		c.22C>A	p.His8Asn	missense	Exon 2 of 6	ENSP00000638972.1

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	0.081
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.078	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0092	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		6.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.25
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.32		Gain of catalytic residue at H8 (P = 0.0941)
MVP		0.31
MPC		0.84
ClinPred		0.94	D
GERP RS		4.6
PromoterAI		0.051	Neutral
Varity_R		0.60
gMVP		0.49
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr5-126253842;