Variant 5-16090966-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001102562.3(MARCHF11):c.809A>G(p.Tyr270Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000376 in 1,461,456 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

MARCHF11
NM_001102562.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

Variant links:

Genes affected

MARCHF11 (HGNC:33609): (membrane associated ring-CH-type finger 11) MARCH11 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). These enzymes add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their intracellular transport. March11 appears to have a role in ubiquitin-mediated protein sorting in the trans-Golgi network (TGN)-multivesicular body (MVB) transport pathway (Morokuma et al., 2007 [PubMed 17604280]).[supplied by OMIM, Apr 2010]

MARCHF11 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCHF11	NM_001102562.3 linkuse as main transcript	c.809A>G	p.Tyr270Cys	missense_variant	3/4	ENST00000332432.9	NP_001096032.1
MARCHF11	XM_047417230.1 linkuse as main transcript	c.694-23173A>G		intron_variant			XP_047273186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCHF11	ENST00000332432.9 linkuse as main transcript	c.809A>G	p.Tyr270Cys	missense_variant	3/4	5	NM_001102562.3	ENSP00000333181	P1	A6NNE9-1
MARCHF11	ENST00000507111.1 linkuse as main transcript	c.105-23173A>G		intron_variant		3		ENSP00000424425
MARCHF11	ENST00000505509.1 linkuse as main transcript	n.390A>G		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248722

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000376

AC:

AN:

1461456

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

727000

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000468

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000827

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2024

The c.809A>G (p.Y270C) alteration is located in exon 3 (coding exon 3) of the MARCH11 gene. This alteration results from a A to G substitution at nucleotide position 809, causing the tyrosine (Y) at amino acid position 270 to be replaced by a cysteine (C). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.036

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.53

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.7

REVEL

Benign

0.24

Sift

Benign

0.15

Sift4G

Uncertain

0.0030

Polyphen

0.99

Vest4

0.74

MutPred

0.46

Gain of catalytic residue at P269 (P = 0.0088);

MVP

0.72

MPC

1.1

ClinPred

0.51

GERP RS

5.5

Varity_R

0.17

gMVP

0.72

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