Variant chr20-3672159-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_025220.5(ADAM33):c.1572G>C(p.Gln524His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,460,090 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

ADAM33
NM_025220.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

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 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
ADAM33	NM_025220.5 link	c.1572G>C	p.Gln524His	missense_variant	Exon 14 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.1572G>C	p.Gln524His	missense_variant	Exon 14 of 22	1	NM_025220.5	ENSP00000348912.3	Q9BZ11-1
ADAM33	ENST00000379861.8 link	c.1572G>C	p.Gln524His	missense_variant	Exon 14 of 22	1		ENSP00000369190.4	A2A2L3
ADAM33	ENST00000466620.5 link	n.1211G>C		non_coding_transcript_exon_variant	Exon 4 of 11	1
ADAM33	ENST00000350009.6 link	c.1572G>C	p.Gln524His	missense_variant	Exon 14 of 21	5		ENSP00000322550.5	Q9BZ11-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248512

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134880

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:

0.0000982

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1460090

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726306

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:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 25, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1572G>C (p.Q524H) alteration is located in exon 14 (coding exon 14) of the ADAM33 gene. This alteration results from a G to C substitution at nucleotide position 1572, causing the glutamine (Q) at amino acid position 524 to be replaced by a histidine (H). 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

0.22

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;.;T;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.68

T;T;T;T

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.44

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;.;.;L

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-4.1

D;D;.;D

REVEL

Benign

0.13

Sift

Uncertain

0.0010

D;D;.;D

Sift4G

Uncertain

0.0030

D;D;T;D

Polyphen

1.0

D;D;.;D

Vest4

0.32

MutPred

0.55

Gain of catalytic residue at Q524 (P = 0.0806);Gain of catalytic residue at Q524 (P = 0.0806);.;Gain of catalytic residue at Q524 (P = 0.0806);

MVP

0.65

MPC

0.069

ClinPred

0.90

GERP RS

4.5

Varity_R

0.59

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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