Genetic Variant MARCHF11:p.Glu131Lys (chr5-16179185-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001102562.3(MARCHF11):c.391G>A(p.Glu131Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00042 in 1,348,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E131D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00045 ( 0 hom. )

Consequence

MARCHF11
NM_001102562.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41

Publications

0 publications found

Variant links:

Genes affected

MARCHF11 (HGNC:33609): (membrane associated ring-CH-type finger 11) MARCH11 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). These enzymes add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their intracellular transport. March11 appears to have a role in ubiquitin-mediated protein sorting in the trans-Golgi network (TGN)-multivesicular body (MVB) transport pathway (Morokuma et al., 2007 [PubMed 17604280]).[supplied by OMIM, Apr 2010]

MARCHF11 links:

MARCHF11-DT (HGNC:55550): (MARCHF11 divergent transcript)

MARCHF11-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10497308).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102562.3. 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
	MARCHF11	NM_001102562.3	MANE Select	c.391G>A	p.Glu131Lys	missense	Exon 1 of 4	NP_001096032.1	A6NNE9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MARCHF11	ENST00000332432.9	TSL:5 MANE Select	c.391G>A	p.Glu131Lys	missense	Exon 1 of 4	ENSP00000333181.7	A6NNE9-1
MARCHF11	ENST00000505509.1	TSL:3	n.119-1304G>A		intron	N/A
MARCHF11-DT	ENST00000757949.1		n.208+3341C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

151704

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000382

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000354

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000416

AC:

AN:

12010

AF XY:

0.000391

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00103

Gnomad NFE exome

AF:

0.000363

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000448

AC:

536

AN:

1197278

Hom.:

Cov.:

AF XY:

0.000451

AC XY:

263

AN XY:

583388

show subpopulations

African (AFR)

AF:

0.0000845

AC:

AN:

23658

American (AMR)

AF:

0.0000955

AC:

AN:

10468

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16526

East Asian (EAS)

AF:

0.00

AC:

AN:

26790

South Asian (SAS)

AF:

0.000227

AC:

AN:

48488

European-Finnish (FIN)

AF:

0.000814

AC:

AN:

28262

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3334

European-Non Finnish (NFE)

AF:

0.000490

AC:

486

AN:

990906

Other (OTH)

AF:

0.000266

AC:

AN:

48846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

109

146

182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000204

AC:

AN:

151704

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

AN XY:

74088

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41388

American (AMR)

AF:

0.00

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000382

AC:

AN:

10468

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.000354

AC:

AN:

67884

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

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:

0.000212

Hom.:

Bravo

AF:

0.000174

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

Benign

0.15

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.57

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

1.4

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.84

REVEL

Benign

0.029

Sift

Benign

0.046

Sift4G

Benign

0.60

Polyphen

0.84

Vest4

0.18

MutPred

0.41

Gain of MoRF binding (P = 0.0042)

MVP

0.43

MPC

0.63

ClinPred

0.12

GERP RS

2.3

Varity_R

0.088

gMVP

0.33

Mutation Taster

=90/10

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