Genetic Variant MARCHF7:p.Ser28Arg (chr2-159729106-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001282805.2(MARCHF7):c.84C>A(p.Ser28Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000322 in 1,610,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

MARCHF7
NM_001282805.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.666

Publications

2 publications found

Variant links:

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]

MARCHF7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.039598852).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MARCHF7	NM_001282805.2	MANE Select	c.84C>A	p.Ser28Arg	missense	Exon 4 of 12	NP_001269734.1	Q9H992-1
MARCHF7	NM_001376234.1		c.84C>A	p.Ser28Arg	missense	Exon 3 of 11	NP_001363163.1	Q9H992-1
MARCHF7	NM_001376235.1		c.84C>A	p.Ser28Arg	missense	Exon 4 of 12	NP_001363164.1	Q9H992-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MARCHF7	ENST00000409175.6	TSL:2 MANE Select	c.84C>A	p.Ser28Arg	missense	Exon 4 of 12	ENSP00000386830.1	Q9H992-1
MARCHF7	ENST00000259050.8	TSL:1	c.84C>A	p.Ser28Arg	missense	Exon 2 of 10	ENSP00000259050.3	Q9H992-1
MARCHF7	ENST00000966712.1		c.84C>A	p.Ser28Arg	missense	Exon 3 of 12	ENSP00000636771.1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000192

AC:

AN:

249360

AF XY:

0.000223

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000415

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000340

AC:

496

AN:

1458886

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

234

AN XY:

725816

show subpopulations

African (AFR)

AF:

0.0000900

AC:

AN:

33350

American (AMR)

AF:

0.00

AC:

AN:

44324

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.00

AC:

AN:

39576

South Asian (SAS)

AF:

0.00

AC:

AN:

85804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5364

European-Non Finnish (NFE)

AF:

0.000429

AC:

477

AN:

1110730

Other (OTH)

AF:

0.000266

AC:

AN:

60246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000151

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41414

American (AMR)

AF:

0.0000655

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000256

Hom.:

Bravo

AF:

0.000159

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000231

AC:

EpiCase

AF:

0.000274

EpiControl

AF:

0.000476

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.017

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.85

M_CAP

Benign

0.012

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

0.67

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.80

REVEL

Benign

0.099

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.053

Polyphen

0.0010

Vest4

0.34

MutPred

0.16

Loss of phosphorylation at S28 (P = 0.0028)

MVP

0.24

MPC

0.070

ClinPred

0.11

GERP RS

4.0

Varity_R

0.12

gMVP

0.25

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over