Variant chr16-71626291-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_052858.6(MARVELD3):c.62G>T(p.Arg21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,541,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000079 ( 0 hom. )

Consequence

MARVELD3
NM_052858.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.166

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0097438395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MARVELD3	NM_052858.6 linkuse as main transcript	c.62G>T	p.Arg21Leu	missense_variant	1/3	ENST00000268485.8
MARVELD3	NM_001017967.4 linkuse as main transcript	c.62G>T	p.Arg21Leu	missense_variant	1/3
MARVELD3	NM_001271329.2 linkuse as main transcript	c.62G>T	p.Arg21Leu	missense_variant	1/3
MARVELD3	XM_011523449.4 linkuse as main transcript	c.62G>T	p.Arg21Leu	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARVELD3	ENST00000268485.8 linkuse as main transcript	c.62G>T	p.Arg21Leu	missense_variant	1/3	1	NM_052858.6	P2	Q96A59-1
	ENST00000562763.1 linkuse as main transcript	n.219+307C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000661

AC:

AN:

151294

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000525

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:

0.000482

GnomAD3 exomes

AF:

0.0000212

AC:

AN:

141308

Hom.:

AF XY:

0.0000131

AC XY:

AN XY:

76272

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000415

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:

0.000487

GnomAD4 exome

AF:

0.00000791

AC:

AN:

1390338

Hom.:

Cov.:

AF XY:

0.00000730

AC XY:

AN XY:

684780

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000199

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:

9.30e-7

Gnomad4 OTH exome

AF:

0.0000522

GnomAD4 genome

AF:

0.0000660

AC:

AN:

151414

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74048

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.000524

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:

0.000477

Alfa

AF:

0.0000304

Hom.:

Bravo

AF:

0.000212

ExAC

AF:

0.0000132

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

Jan 24, 2023

The c.62G>T (p.R21L) alteration is located in exon 1 (coding exon 1) of the MARVELD3 gene. This alteration results from a G to T substitution at nucleotide position 62, causing the arginine (R) at amino acid position 21 to be replaced by a leucine (L). 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

0.16

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.079

T;.;T;.

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.61

T;T;T;T

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.0097

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.1

.;M;M;M

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.79

PROVEAN

Pathogenic

-6.4

.;D;D;D

REVEL

Benign

0.049

Sift

Pathogenic

0.0

.;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

0.22, 0.062

.;.;B;B

Vest4

0.14

MutPred

0.46

Loss of MoRF binding (P = 0.0224);Loss of MoRF binding (P = 0.0224);Loss of MoRF binding (P = 0.0224);Loss of MoRF binding (P = 0.0224);

MVP

0.33

MPC

0.28

ClinPred

0.30

GERP RS

1.9

Varity_R

0.20

gMVP

0.40

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