Variant rs3764990 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001282866.2(MARCHF8):c.1120C>T(p.Pro374Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.062 in 1,592,906 control chromosomes in the GnomAD database, including 3,422 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.049 ( 255 hom., cov: 33)

Exomes 𝑓: 0.063 ( 3167 hom. )

Consequence

MARCHF8
NM_001282866.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.03

Variant links:

Genes affected

MARCHF8 (HGNC:23356): (membrane associated ring-CH-type finger 8) MARCH8 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. MARCH8 induces the internalization of several membrane glycoproteins (Goto et al., 2003 [PubMed 12582153]; Bartee et al., 2004 [PubMed 14722266]).[supplied by OMIM, Apr 2010]

MARCHF8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0141607225).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MARCHF8	NM_001282866.2 linkuse as main transcript	c.1120C>T	p.Pro374Ser	missense_variant	6/8	ENST00000453424.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARCHF8	ENST00000453424.7 linkuse as main transcript	c.1120C>T	p.Pro374Ser	missense_variant	6/8	1	NM_001282866.2		Q5T0T0-2

Frequencies

GnomAD3 genomes

AF:

0.0488

AC:

7422

AN:

152110

Hom.:

252

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0193

Gnomad AMI

AF:

0.0648

Gnomad AMR

AF:

0.0450

Gnomad ASJ

AF:

0.0400

Gnomad EAS

AF:

0.0517

Gnomad SAS

AF:

0.0211

Gnomad FIN

AF:

0.0692

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0664

Gnomad OTH

AF:

0.0464

GnomAD3 exomes

AF:

0.0503

AC:

11627

AN:

231222

Hom.:

366

AF XY:

0.0499

AC XY:

6271

AN XY:

125718

show subpopulations

Gnomad AFR exome

AF:

0.0182

Gnomad AMR exome

AF:

0.0305

Gnomad ASJ exome

AF:

0.0359

Gnomad EAS exome

AF:

0.0416

Gnomad SAS exome

AF:

0.0237

Gnomad FIN exome

AF:

0.0785

Gnomad NFE exome

AF:

0.0641

Gnomad OTH exome

AF:

0.0524

GnomAD4 exome

AF:

0.0634

AC:

91379

AN:

1440678

Hom.:

3167

Cov.:

AF XY:

0.0623

AC XY:

44666

AN XY:

716670

show subpopulations

Gnomad4 AFR exome

AF:

0.0197

Gnomad4 AMR exome

AF:

0.0301

Gnomad4 ASJ exome

AF:

0.0378

Gnomad4 EAS exome

AF:

0.0862

Gnomad4 SAS exome

AF:

0.0227

Gnomad4 FIN exome

AF:

0.0771

Gnomad4 NFE exome

AF:

0.0687

Gnomad4 OTH exome

AF:

0.0555

GnomAD4 genome

AF:

0.0488

AC:

7422

AN:

152228

Hom.:

255

Cov.:

AF XY:

0.0491

AC XY:

3657

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0195

Gnomad4 AMR

AF:

0.0450

Gnomad4 ASJ

AF:

0.0400

Gnomad4 EAS

AF:

0.0516

Gnomad4 SAS

AF:

0.0209

Gnomad4 FIN

AF:

0.0692

Gnomad4 NFE

AF:

0.0664

Gnomad4 OTH

AF:

0.0459

Alfa

AF:

0.0557

Hom.:

138

Bravo

AF:

0.0456

TwinsUK

AF:

0.0693

AC:

257

ALSPAC

AF:

0.0672

AC:

259

ESP6500AA

AF:

0.0188

AC:

ESP6500EA

AF:

0.0603

AC:

519

ExAC

AF:

0.0501

AC:

6078

Asia WGS

AF:

0.0370

AC:

128

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.39

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.87

LIST_S2

Pathogenic

0.98

D;D;.

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

9.8e-9

P;P;P

PrimateAI

Uncertain

0.72

Sift4G

Uncertain

0.036

D;D;D

Polyphen

0.83

.;P;P

Vest4

0.29

ClinPred

0.024

GERP RS

5.7

Varity_R

0.54

gMVP

0.68

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over