Variant rs7908745 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.1642T>C(p.Tyr548His) variant causes a missense change. The variant allele was found at a frequency of 0.314 in 1,613,644 control chromosomes in the GnomAD database, including 81,200 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.33 ( 8238 hom., cov: 33)

Exomes 𝑓: 0.31 ( 72962 hom. )

Consequence

MARCHF8
NM_001282866.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.32

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:

MARCHF8 (HGNC:):

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=0.0030372143).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCHF8	NM_001282866.2 linkuse as main transcript	c.1642T>C	p.Tyr548His	missense_variant	8/8	ENST00000453424.7	NP_001269795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MARCHF8	ENST00000453424.7 linkuse as main transcript	c.1642T>C	p.Tyr548His	missense_variant	8/8	1	NM_001282866.2	ENSP00000411848.2	Q5T0T0-2
MARCHF8	ENST00000319836.7 linkuse as main transcript	c.796T>C	p.Tyr266His	missense_variant	7/7	1		ENSP00000317087.3	Q5T0T0-1
MARCHF8	ENST00000395769.6 linkuse as main transcript	c.796T>C	p.Tyr266His	missense_variant	7/7	1		ENSP00000379116.2	Q5T0T0-1
MARCHF8	ENST00000476962.1 linkuse as main transcript	n.1347T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49527

AN:

151956

Hom.:

8230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.347

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.377

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.166

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.356

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.326

GnomAD3 exomes

AF:

0.315

AC:

79102

AN:

251366

Hom.:

12939

AF XY:

0.311

AC XY:

42250

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.347

Gnomad AMR exome

AF:

0.402

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.158

Gnomad SAS exome

AF:

0.298

Gnomad FIN exome

AF:

0.362

Gnomad NFE exome

AF:

0.316

Gnomad OTH exome

AF:

0.298

GnomAD4 exome

AF:

0.313

AC:

457886

AN:

1461570

Hom.:

72962

Cov.:

AF XY:

0.311

AC XY:

226439

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.346

Gnomad4 AMR exome

AF:

0.394

Gnomad4 ASJ exome

AF:

0.202

Gnomad4 EAS exome

AF:

0.182

Gnomad4 SAS exome

AF:

0.296

Gnomad4 FIN exome

AF:

0.362

Gnomad4 NFE exome

AF:

0.316

Gnomad4 OTH exome

AF:

0.302

GnomAD4 genome

AF:

0.326

AC:

49556

AN:

152074

Hom.:

8238

Cov.:

AF XY:

0.329

AC XY:

24475

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.347

Gnomad4 AMR

AF:

0.377

Gnomad4 ASJ

AF:

0.198

Gnomad4 EAS

AF:

0.166

Gnomad4 SAS

AF:

0.289

Gnomad4 FIN

AF:

0.356

Gnomad4 NFE

AF:

0.318

Gnomad4 OTH

AF:

0.325

Alfa

AF:

0.312

Hom.:

17464

Bravo

AF:

0.327

TwinsUK

AF:

0.308

AC:

1142

ALSPAC

AF:

0.314

AC:

1212

ESP6500AA

AF:

0.353

AC:

1554

ESP6500EA

AF:

0.304

AC:

2615

ExAC

AF:

0.315

AC:

38187

Asia WGS

AF:

0.279

AC:

973

AN:

3478

EpiCase

AF:

0.313

EpiControl

AF:

0.312

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.0024

.;T;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.066

T;T;.

MetaRNN

Benign

0.0030

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.69

.;N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

0.55

.;N;N

REVEL

Benign

0.064

Sift

Benign

0.59

.;T;T

Sift4G

Benign

0.55

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.031

ClinPred

0.0052

GERP RS

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.021

gMVP

0.27

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