Variant chr20-3671968-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000356518.7(ADAM33):c.1615G>A(p.Glu539Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000983 in 1,555,712 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: 𝑓 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000087 ( 0 hom. )

Consequence

ADAM33
ENST00000356518.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.74

Variant links:

Genes affected

ADAM33 (HGNC:15478): (ADAM metallopeptidase domain 33) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. This protein is a type I transmembrane protein implicated in asthma and bronchial hyperresponsiveness. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]

ADAM33 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.057273358).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM33	NM_025220.5 linkuse as main transcript	c.1615G>A	p.Glu539Lys	missense_variant	15/22	ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518.7 linkuse as main transcript	c.1615G>A	p.Glu539Lys	missense_variant	15/22	1	NM_025220.5	ENSP00000348912	P4	Q9BZ11-1
ADAM33	ENST00000379861.8 linkuse as main transcript	c.1615G>A	p.Glu539Lys	missense_variant	15/22	1		ENSP00000369190	A2
ADAM33	ENST00000466620.5 linkuse as main transcript	n.1254G>A		non_coding_transcript_exon_variant	5/11	1
ADAM33	ENST00000350009.6 linkuse as main transcript	c.1615G>A	p.Glu539Lys	missense_variant	15/21	5		ENSP00000322550	A2	Q9BZ11-2

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000929

AC:

AN:

161436

Hom.:

AF XY:

0.0000469

AC XY:

AN XY:

85338

show subpopulations

Gnomad AFR exome

AF:

0.000654

Gnomad AMR exome

AF:

0.0000799

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000432

Gnomad FIN exome

AF:

0.000193

Gnomad NFE exome

AF:

0.0000472

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000869

AC:

122

AN:

1403368

Hom.:

Cov.:

AF XY:

0.0000823

AC XY:

AN XY:

692620

show subpopulations

Gnomad4 AFR exome

AF:

0.000877

Gnomad4 AMR exome

AF:

0.0000556

Gnomad4 ASJ exome

AF:

0.0000397

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.0000610

Gnomad4 NFE exome

AF:

0.0000731

Gnomad4 OTH exome

AF:

0.000120

GnomAD4 genome

AF:

0.000203

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000702

Hom.:

Bravo

AF:

0.000276

ESP6500AA

AF:

0.000231

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.0000626

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Jul 14, 2021

The c.1615G>A (p.E539K) alteration is located in exon 15 (coding exon 15) of the ADAM33 gene. This alteration results from a G to A substitution at nucleotide position 1615, causing the glutamic acid (E) at amino acid position 539 to be replaced by a lysine (K). 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

0.079

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.093

T;.;T;.

Eigen

Benign

0.053

Eigen_PC

Benign

-0.0095

FATHMM_MKL

Benign

0.21

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.065

MetaRNN

Benign

0.057

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.;.;L

MutationTaster

Benign

0.96

N;N;N

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.5

N;N;.;N

REVEL

Benign

0.11

Sift

Benign

0.054

T;T;.;T

Sift4G

Benign

0.14

T;T;T;T

Polyphen

1.0

D;D;.;D

Vest4

0.23

MVP

0.53

MPC

0.34

ClinPred

0.088

GERP RS

4.3

Varity_R

0.38

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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