Variant rs781061959 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152598.4(MARCHF10):c.1957G>A(p.Glu653Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000169 in 1,599,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

MARCHF10
NM_152598.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.82

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16014853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCHF10	NM_152598.4 link	c.1957G>A	p.Glu653Lys	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.1957G>A	p.Glu653Lys	missense_variant	Exon 7 of 11	2	NM_152598.4	ENSP00000311496.5		Q8NA82

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000896

AC:

AN:

234410

Hom.:

AF XY:

0.0000707

AC XY:

AN XY:

127272

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00106

Gnomad SAS exome

AF:

0.0000726

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000917

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000152

AC:

AN:

1447362

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

720012

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000334

Gnomad4 SAS exome

AF:

0.0000359

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.0000334

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1957G>A (p.E653K) alteration is located in exon 7 (coding exon 6) of the MARCH10 gene. This alteration results from a G to A substitution at nucleotide position 1957, causing the glutamic acid (E) at amino acid position 653 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

.;T;T;.;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;.;D;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.16

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

.;M;M;.;.

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.4

.;D;D;.;D

REVEL

Benign

0.23

Sift

Uncertain

0.0020

.;D;D;.;D

Sift4G

Uncertain

0.011

D;D;D;D;D

Polyphen

1.0

.;D;D;.;D

Vest4

0.40, 0.44, 0.43, 0.44

MutPred

0.33

.;Gain of ubiquitination at E653 (P = 0.0029);Gain of ubiquitination at E653 (P = 0.0029);.;.;

MVP

0.58

MPC

0.64

ClinPred

0.61

GERP RS

4.4

Varity_R

0.48

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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