chr2-159729104-A-C

Variant names:

• chr2-159729104-A-C
• NM_001282805.2:c.82A>C
• MARCHF7 p.Ser28Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001282805.2(MARCHF7):​c.82A>C​(p.Ser28Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MARCHF7 NM_001282805.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.47
• Publications: 0 publications found

Genes affected

MARCHF7 (HGNC:17393): (membrane associated ring-CH-type finger 7) MARCH7 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH proteins add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments (Bartee et al., 2004 [PubMed 14722266]).[supplied by OMIM, Mar 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13141856).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282805.2. 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
	MARCHF7	NM_001282805.2	MANE Select	c.82A>C	p.Ser28Arg	missense	Exon 4 of 12	NP_001269734.1	Q9H992-1
	MARCHF7	NM_001376234.1		c.82A>C	p.Ser28Arg	missense	Exon 3 of 11	NP_001363163.1	Q9H992-1
	MARCHF7	NM_001376235.1		c.82A>C	p.Ser28Arg	missense	Exon 4 of 12	NP_001363164.1	Q9H992-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF7	ENST00000409175.6	TSL:2 MANE Select	c.82A>C	p.Ser28Arg	missense	Exon 4 of 12	ENSP00000386830.1	Q9H992-1
	MARCHF7	ENST00000259050.8	TSL:1	c.82A>C	p.Ser28Arg	missense	Exon 2 of 10	ENSP00000259050.3	Q9H992-1
	MARCHF7	ENST00000966712.1		c.82A>C	p.Ser28Arg	missense	Exon 3 of 12	ENSP00000636771.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.017	T
Eigen	Benign	0.0068
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.5
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.042
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.053	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.25
Mutation Taster		=93/7	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-160585615;