Variant 16-71626350-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_052858.6(MARVELD3):c.121C>A(p.Pro41Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MARVELD3
NM_052858.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.895

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05124849).

BP6

Variant 16-71626350-C-A is Benign according to our data. Variant chr16-71626350-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2316870.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MARVELD3	NM_052858.6 linkuse as main transcript	c.121C>A	p.Pro41Thr	missense_variant	1/3	ENST00000268485.8
MARVELD3	NM_001017967.4 linkuse as main transcript	c.121C>A	p.Pro41Thr	missense_variant	1/3
MARVELD3	NM_001271329.2 linkuse as main transcript	c.121C>A	p.Pro41Thr	missense_variant	1/3
MARVELD3	XM_011523449.4 linkuse as main transcript	c.121C>A	p.Pro41Thr	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARVELD3	ENST00000268485.8 linkuse as main transcript	c.121C>A	p.Pro41Thr	missense_variant	1/3	1	NM_052858.6	P2	Q96A59-1
	ENST00000562763.1 linkuse as main transcript	n.219+248G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1396022

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

688504

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.2

DANN

Benign

0.82

DEOGEN2

Benign

0.025

T;.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.37

T;T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.051

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;L;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-4.2

.;D;N;N

REVEL

Benign

0.015

Sift

Benign

0.11

.;T;T;T

Sift4G

Benign

0.17

T;T;T;T

Polyphen

0.0020, 0.0010

.;.;B;B

Vest4

0.042

MutPred

0.25

Gain of phosphorylation at P41 (P = 4e-04);Gain of phosphorylation at P41 (P = 4e-04);Gain of phosphorylation at P41 (P = 4e-04);Gain of phosphorylation at P41 (P = 4e-04);

MVP

0.014

MPC

0.25

ClinPred

0.051

GERP RS

0.82

Varity_R

0.049

gMVP

0.23

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over