Variant chr16-71626664-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052858.6(MARVELD3):c.435G>T(p.Arg145Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000308 in 1,524,140 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 1 hom. )

Consequence

MARVELD3
NM_052858.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.274

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MARVELD3	NM_052858.6 linkuse as main transcript	c.435G>T	p.Arg145Ser	missense_variant	1/3	ENST00000268485.8
MARVELD3	NM_001017967.4 linkuse as main transcript	c.435G>T	p.Arg145Ser	missense_variant	1/3
MARVELD3	XM_011523449.4 linkuse as main transcript	c.435G>T	p.Arg145Ser	missense_variant	1/3
MARVELD3	NM_001271329.2 linkuse as main transcript	c.304+131G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARVELD3	ENST00000268485.8 linkuse as main transcript	c.435G>T	p.Arg145Ser	missense_variant	1/3	1	NM_052858.6	P2	Q96A59-1
	ENST00000562763.1 linkuse as main transcript	n.153C>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000125

AC:

AN:

119786

Hom.:

AF XY:

0.000137

AC XY:

AN XY:

65542

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000631

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:

0.0000229

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000153

AC:

AN:

1372070

Hom.:

Cov.:

AF XY:

0.0000163

AC XY:

AN XY:

675834

show subpopulations

Gnomad4 AFR exome

AF:

0.0000325

Gnomad4 AMR exome

AF:

0.000362

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:

0.00000653

Gnomad4 OTH exome

AF:

0.0000176

GnomAD4 genome

AF:

0.000171

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.000170

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

Jun 13, 2024

The c.435G>T (p.R145S) 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 435, causing the arginine (R) at amino acid position 145 to be replaced by a serine (S). 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

0.23

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.054

T;T;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.51

T;T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.086

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.0

.;M;M

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.8

.;N;N

REVEL

Benign

0.052

Sift

Uncertain

0.011

.;D;D

Sift4G

Uncertain

0.018

D;D;D

Polyphen

0.88

.;P;P

Vest4

0.18

MutPred

0.29

Gain of glycosylation at R145 (P = 0.0061);Gain of glycosylation at R145 (P = 0.0061);Gain of glycosylation at R145 (P = 0.0061);

MVP

0.43

MPC

0.48

ClinPred

0.074

GERP RS

1.1

Varity_R

0.17

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.33

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.33

Position offset: -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