16-71626261-G-C

Variant names:

• chr16-71626261-G-C
• rs763736205
• NM_052858.6:c.32G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_052858.6(MARVELD3):​c.32G>C​(p.Arg11Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R11Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MARVELD3 NM_052858.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.52
• Publications: 0 publications found

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]

ENSG00000260593 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARVELD3	NM_052858.6	c.32G>C	p.Arg11Pro	missense_variant	Exon 1 of 3	ENST00000268485.8	NP_443090.4
MARVELD3	NM_001017967.4	c.32G>C	p.Arg11Pro	missense_variant	Exon 1 of 3		NP_001017967.2
MARVELD3	NM_001271329.2	c.32G>C	p.Arg11Pro	missense_variant	Exon 1 of 3		NP_001258258.1
MARVELD3	XM_011523449.4	c.32G>C	p.Arg11Pro	missense_variant	Exon 1 of 3		XP_011521751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARVELD3	ENST00000268485.8	c.32G>C	p.Arg11Pro	missense_variant	Exon 1 of 3	1	NM_052858.6	ENSP00000268485.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 61

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.32G>C (p.R11P) alteration is located in exon 1 (coding exon 1) of the MARVELD3 gene. This alteration results from a G to C substitution at nucleotide position 32, causing the arginine (R) at amino acid position 11 to be replaced by a proline (P). 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	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Benign	0.88
DEOGEN2	Benign	0.12	T;.;T;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.57	T;T;T;T
M_CAP	Pathogenic	0.73	D
MetaRNN	Uncertain	0.58	D;D;D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.0	.;M;M;M
PhyloP100		2.5
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-5.7	.;D;D;D
REVEL	Benign	0.26
Sift	Pathogenic	0.0	.;D;D;D
Sift4G	Uncertain	0.043	D;T;D;T
Polyphen		1.0	.;.;D;D
Vest4		0.36
MutPred		0.40		Loss of MoRF binding (P = 0.0053);Loss of MoRF binding (P = 0.0053);Loss of MoRF binding (P = 0.0053);Loss of MoRF binding (P = 0.0053);
MVP		0.41
MPC		0.32
ClinPred		1.0	D
GERP RS		4.1
PromoterAI		-0.031	Neutral
Varity_R		0.59
gMVP		0.45

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

Other links and lift over

dbSNP: rs763736205; hg19: chr16-71660164;