Variant 20-3671667-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_025220.5(ADAM33):c.1819C>G(p.Arg607Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 1,582,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

ADAM33
NM_025220.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.584

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.751

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM33	NM_025220.5 link	c.1819C>G	p.Arg607Gly	missense_variant	Exon 16 of 22	ENST00000356518.7	NP_079496.1	Q9BZ11-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADAM33	ENST00000356518.7 link	c.1819C>G	p.Arg607Gly	missense_variant	Exon 16 of 22	1	NM_025220.5	ENSP00000348912.3	Q9BZ11-1
ADAM33	ENST00000379861.8 link	c.1819C>G	p.Arg607Gly	missense_variant	Exon 16 of 22	1		ENSP00000369190.4	A2A2L3
ADAM33	ENST00000466620.5 link	n.1458C>G		non_coding_transcript_exon_variant	Exon 6 of 11	1
ADAM33	ENST00000350009.6 link	c.1819C>G	p.Arg607Gly	missense_variant	Exon 16 of 21	5		ENSP00000322550.5	Q9BZ11-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000503

AC:

AN:

198660

Hom.:

AF XY:

0.00

AC XY:

AN XY:

107222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000118

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1429994

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

708960

show subpopulations

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:

9.13e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000251

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

T;.;T;.

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.012

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.84

T;T;T;T

M_CAP

Benign

0.069

MetaRNN

Pathogenic

0.75

D;D;D;D

MetaSVM

Benign

-0.87

MutationAssessor

Pathogenic

3.0

M;.;.;M

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-6.2

D;D;.;D

REVEL

Benign

0.17

Sift

Uncertain

0.0010

D;D;.;D

Sift4G

Uncertain

0.0090

D;D;D;D

Polyphen

0.97

D;D;.;D

Vest4

0.61

MutPred

0.69

Loss of methylation at R607 (P = 0.0778);Loss of methylation at R607 (P = 0.0778);.;Loss of methylation at R607 (P = 0.0778);

MVP

0.48

MPC

0.34

ClinPred

0.98

GERP RS

1.9

Varity_R

0.68

gMVP

0.94

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over