Variant 17-62736189-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_152598.4(MARCHF10):c.1679C>T(p.Thr560Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00804 in 1,614,200 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0073 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 71 hom. )

Consequence

MARCHF10
NM_152598.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.58

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:):

ENSG00000265702 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032739043).

BP6

Variant 17-62736189-G-A is Benign according to our data. Variant chr17-62736189-G-A is described in ClinVar as [Benign]. Clinvar id is 3056124.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCHF10	NM_152598.4 linkuse as main transcript	c.1679C>T	p.Thr560Ile	missense_variant	6/11	ENST00000311269.10	NP_689811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCHF10	ENST00000311269.10 linkuse as main transcript	c.1679C>T	p.Thr560Ile	missense_variant	6/11	2	NM_152598.4	ENSP00000311496.5		Q8NA82

Frequencies

GnomAD3 genomes

AF:

0.00733

AC:

1116

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0140

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00518

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00992

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00717

AC:

1800

AN:

251016

Hom.:

AF XY:

0.00752

AC XY:

1020

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.000924

Gnomad AMR exome

AF:

0.00804

Gnomad ASJ exome

AF:

0.0119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00591

Gnomad FIN exome

AF:

0.00416

Gnomad NFE exome

AF:

0.00930

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.00811

AC:

11856

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00807

AC XY:

5872

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.00861

Gnomad4 ASJ exome

AF:

0.0108

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00569

Gnomad4 FIN exome

AF:

0.00406

Gnomad4 NFE exome

AF:

0.00894

Gnomad4 OTH exome

AF:

0.00750

GnomAD4 genome

AF:

0.00732

AC:

1115

AN:

152322

Hom.:

Cov.:

AF XY:

0.00737

AC XY:

549

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.0140

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00518

Gnomad4 NFE

AF:

0.00992

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00873

Hom.:

Bravo

AF:

0.00756

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00965

AC:

ExAC

AF:

0.00670

AC:

814

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0123

EpiControl

AF:

0.0122

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MARCHF10-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 29, 2019

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

Benign

0.18

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.45

DEOGEN2

Benign

0.0038

.;T;T;.;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.69

T;.;T;T;T

M_CAP

Benign

0.00075

MetaRNN

Benign

0.0033

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L;L;.;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.8

.;N;N;.;N

REVEL

Benign

0.020

Sift

Benign

0.19

.;T;T;.;T

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

0.14, 0.23

.;B;B;.;B

Vest4

0.048, 0.030, 0.13, 0.050

MVP

0.17

MPC

0.16

ClinPred

0.0033

GERP RS

3.3

Varity_R

0.060

gMVP

0.34

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