17-62725057-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 3P and 13B. PM1PP3BP4_StrongBP6BS1BS2

The NM_152598.4(MARCHF10):c.1985G>A(p.Cys662Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,606,550 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0058 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00064 ( 8 hom. )

Consequence

MARCHF10
NM_152598.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.91

Variant links:

Genes affected

MARCHF10 (HGNC:26655): (membrane associated ring-CH-type finger 10) MARCH10 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH enzymes add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments (Morokuma et al., 2007 [PubMed 17604280]).[supplied by OMIM, Apr 2010]

MARCHF10 links:

ENSG00000265702 (HGNC:58173):

ENSG00000265702 links:

LOC105371855 (HGNC:):

LOC105371855 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity MARHA_HUMAN

PP3

Multiple lines of computational evidence support a deleterious effect 9: AlphaMissense, BayesDel_noAF, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, PrimateAI, PROVEAN, REVEL [when Dann, max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.016122937).

BP6

Variant 17-62725057-C-T is Benign according to our data. Variant chr17-62725057-C-T is described in ClinVar as [Benign]. Clinvar id is 3053092.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00582 (887/152350) while in subpopulation AFR AF= 0.02 (833/41584). AF 95% confidence interval is 0.0189. There are 4 homozygotes in gnomad4. There are 426 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCHF10	NM_152598.4 link	c.1985G>A	p.Cys662Tyr	missense_variant	Exon 7 of 11	ENST00000311269.10	NP_689811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCHF10	ENST00000311269.10 link	c.1985G>A	p.Cys662Tyr	missense_variant	Exon 7 of 11	2	NM_152598.4	ENSP00000311496.5		Q8NA82

Frequencies

GnomAD3 genomes

AF:

0.00583

AC:

887

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0201

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00163

AC:

396

AN:

242516

Hom.:

AF XY:

0.00113

AC XY:

149

AN XY:

131442

show subpopulations

Gnomad AFR exome

AF:

0.0213

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000897

Gnomad OTH exome

AF:

0.000864

GnomAD4 exome

AF:

0.000637

AC:

926

AN:

1454200

Hom.:

Cov.:

AF XY:

0.000570

AC XY:

412

AN XY:

723428

show subpopulations

Gnomad4 AFR exome

AF:

0.0203

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000919

Gnomad4 OTH exome

AF:

0.00140

GnomAD4 genome

AF:

0.00582

AC:

887

AN:

152350

Hom.:

Cov.:

AF XY:

0.00572

AC XY:

426

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0200

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00122

Hom.:

Bravo

AF:

0.00660

ESP6500AA

AF:

0.0193

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00209

AC:

254

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MARCHF10-related disorder

Benign:1

Feb 22, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Pathogenic

0.41

CADD

Pathogenic

DANN

Benign

0.93

DEOGEN2

Benign

0.31

.;T;T;.;.

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.93

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;.;D;D;D

MetaRNN

Benign

0.016

T;T;T;T;T

MetaSVM

Uncertain

0.65

MutationAssessor

Pathogenic

4.5

.;H;H;.;.

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-11

.;D;D;.;D

REVEL

Pathogenic

0.91

Sift

Pathogenic

0.0

.;D;D;.;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

.;D;D;.;D

Vest4

0.86, 0.86, 0.90, 0.89

MVP

0.77

MPC

0.79

ClinPred

0.19

GERP RS

5.4

Varity_R

0.94

gMVP

0.97

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over