Variant 16-71626297-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052858.6(MARVELD3):c.68C>T(p.Pro23Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000287 in 1,394,404 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

MARVELD3
NM_052858.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.131

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22023019).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MARVELD3	NM_052858.6 linkuse as main transcript	c.68C>T	p.Pro23Leu	missense_variant	1/3	ENST00000268485.8
MARVELD3	NM_001017967.4 linkuse as main transcript	c.68C>T	p.Pro23Leu	missense_variant	1/3
MARVELD3	NM_001271329.2 linkuse as main transcript	c.68C>T	p.Pro23Leu	missense_variant	1/3
MARVELD3	XM_011523449.4 linkuse as main transcript	c.68C>T	p.Pro23Leu	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARVELD3	ENST00000268485.8 linkuse as main transcript	c.68C>T	p.Pro23Leu	missense_variant	1/3	1	NM_052858.6	P2	Q96A59-1
	ENST00000562763.1 linkuse as main transcript	n.219+301G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000287

AC:

AN:

1394404

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

687300

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

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.:

Bravo

AF:

0.00000378

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

Aug 16, 2021

The c.68C>T (p.P23L) alteration is located in exon 1 (coding exon 1) of the MARVELD3 gene. This alteration results from a C to T substitution at nucleotide position 68, causing the proline (P) at amino acid position 23 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

0.13

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.11

T;.;T;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.59

T;T;T;T

M_CAP

Pathogenic

0.71

MetaRNN

Benign

0.22

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.0

.;M;M;M

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-7.3

.;D;D;D

REVEL

Benign

0.17

Sift

Pathogenic

0.0

.;D;D;D

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.38, 0.22

.;.;B;B

Vest4

0.074

MutPred

0.38

Gain of catalytic residue at P23 (P = 0.0085);Gain of catalytic residue at P23 (P = 0.0085);Gain of catalytic residue at P23 (P = 0.0085);Gain of catalytic residue at P23 (P = 0.0085);

MVP

0.47

MPC

0.23

ClinPred

0.60

GERP RS

4.1

Varity_R

0.054

gMVP

0.31

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