16-71626261-G-A

Position:

chr16-71626261-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_052858.6(MARVELD3):c.32G>A(p.Arg11Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000249 in 1,526,402 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R11P) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

MARVELD3
NM_052858.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52

Variant links:

Genes affected

MARVELD3 (HGNC:30525): (MARVEL domain containing 3) Enables mitogen-activated protein kinase kinase kinase binding activity. Involved in bicellular tight junction assembly. Acts upstream of or within several processes, including negative regulation of JNK cascade; negative regulation of epithelial cell migration; and negative regulation of epithelial cell proliferation. Located in bicellular tight junction and cytoplasmic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

MARVELD3 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28752667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MARVELD3	NM_052858.6 linkuse as main transcript	c.32G>A	p.Arg11Gln	missense_variant	1/3	ENST00000268485.8
MARVELD3	NM_001017967.4 linkuse as main transcript	c.32G>A	p.Arg11Gln	missense_variant	1/3
MARVELD3	NM_001271329.2 linkuse as main transcript	c.32G>A	p.Arg11Gln	missense_variant	1/3
MARVELD3	XM_011523449.4 linkuse as main transcript	c.32G>A	p.Arg11Gln	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARVELD3	ENST00000268485.8 linkuse as main transcript	c.32G>A	p.Arg11Gln	missense_variant	1/3	1	NM_052858.6	P2	Q96A59-1
	ENST00000562763.1 linkuse as main transcript	n.219+337C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151740

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000142

AC:

AN:

126316

Hom.:

AF XY:

0.000174

AC XY:

AN XY:

68770

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000854

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000240

AC:

AN:

1374662

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

676258

show subpopulations

Gnomad4 AFR exome

AF:

0.0000654

Gnomad4 AMR exome

AF:

0.000660

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000131

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000468

Gnomad4 OTH exome

AF:

0.0000529

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151740

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74116

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000718

ExAC

AF:

0.0000322

AC:

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

Apr 25, 2022

The c.32G>A (p.R11Q) alteration is located in exon 1 (coding exon 1) of the MARVELD3 gene. This alteration results from a G to A substitution at nucleotide position 32, causing the arginine (R) at amino acid position 11 to be replaced by a glutamine (Q). 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

0.18

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.049

T;.;T;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.68

T;T;T;T

M_CAP

Pathogenic

0.72

MetaRNN

Benign

0.29

T;T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Uncertain

2.0

.;M;M;M

MutationTaster

Benign

0.91

N;N;N;N

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-3.0

.;D;N;N

REVEL

Benign

0.17

Sift

Pathogenic

0.0

.;D;D;D

Sift4G

Uncertain

0.015

D;D;D;T

Polyphen

1.0

.;.;D;D

Vest4

0.094

MutPred

0.36

Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);

MVP

0.37

MPC

0.26

ClinPred

0.41

GERP RS

4.1

Varity_R

0.37

gMVP

0.36

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