Variant 16-71626336-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_052858.6(MARVELD3):c.107A>T(p.Asp36Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,396,054 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

MARVELD3
NM_052858.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.255

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:

ENSG00000260593 (HGNC:):

ENSG00000260593 links:

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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=0.2814271).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARVELD3	NM_052858.6 link	c.107A>T	p.Asp36Val	missense_variant	1/3	ENST00000268485.8	NP_443090.4	Q96A59-1
MARVELD3	NM_001017967.4 link	c.107A>T	p.Asp36Val	missense_variant	1/3		NP_001017967.2	Q96A59-2
MARVELD3	NM_001271329.2 link	c.107A>T	p.Asp36Val	missense_variant	1/3		NP_001258258.1	Q96A59-3
MARVELD3	XM_011523449.4 link	c.107A>T	p.Asp36Val	missense_variant	1/3		XP_011521751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARVELD3	ENST00000268485.8 link	c.107A>T	p.Asp36Val	missense_variant	1/3	1	NM_052858.6	ENSP00000268485.3		Q96A59-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000672

AC:

AN:

148722

Hom.:

AF XY:

0.0000126

AC XY:

AN XY:

79488

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000129

AC:

AN:

1396054

Hom.:

Cov.:

AF XY:

0.00000726

AC XY:

AN XY:

688540

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000280

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:

0.0000148

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000566

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.000259

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000129

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

Sep 09, 2024

The c.107A>T (p.D36V) alteration is located in exon 1 (coding exon 1) of the MARVELD3 gene. This alteration results from a A to T substitution at nucleotide position 107, causing the aspartic acid (D) at amino acid position 36 to be replaced by a valine (V). 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

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.14

T;.;T;.

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.58

T;T;T;T

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.28

T;T;T;T

MetaSVM

Benign

-0.54

MutationAssessor

Benign

1.9

.;L;L;L

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-7.1

.;D;D;D

REVEL

Benign

0.16

Sift

Pathogenic

0.0

.;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;D

Polyphen

0.99, 1.0

.;.;D;D

Vest4

0.21

MVP

0.48

MPC

0.32

ClinPred

0.84

GERP RS

4.2

Varity_R

0.40

gMVP

0.39

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