Variant 17-62725011-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_152598.4(MARCHF10):c.2031C>T(p.Cys677Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00467 in 1,610,320 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0028 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 22 hom. )

Consequence

MARCHF10
NM_152598.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.793

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 17-62725011-G-A is Benign according to our data. Variant chr17-62725011-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3038174.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.793 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCHF10	NM_152598.4 linkuse as main transcript	c.2031C>T	p.Cys677Cys	synonymous_variant	7/11	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.2031C>T	p.Cys677Cys	synonymous_variant	7/11	2	NM_152598.4	ENSP00000311496.5		Q8NA82

Frequencies

GnomAD3 genomes

AF:

0.00277

AC:

422

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00475

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00236

AC:

582

AN:

246700

Hom.:

AF XY:

0.00226

AC XY:

302

AN XY:

133468

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.00161

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00435

Gnomad OTH exome

AF:

0.00168

GnomAD4 exome

AF:

0.00487

AC:

7105

AN:

1458004

Hom.:

Cov.:

AF XY:

0.00467

AC XY:

3389

AN XY:

725246

show subpopulations

Gnomad4 AFR exome

AF:

0.000480

Gnomad4 AMR exome

AF:

0.00198

Gnomad4 ASJ exome

AF:

0.0000767

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.000281

Gnomad4 NFE exome

AF:

0.00611

Gnomad4 OTH exome

AF:

0.00315

GnomAD4 genome

AF:

0.00277

AC:

422

AN:

152316

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

170

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00475

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00287

Hom.:

Bravo

AF:

0.00299

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MARCHF10-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 08, 2019

This variant is classified as likely 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

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.1

DANN

Benign

0.83

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