20-3672148-T-C

Variant names:

• chr20-3672148-T-C
• rs776168462
• NM_025220.5:c.1583A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025220.5(ADAM33):​c.1583A>G​(p.Gln528Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ADAM33 NM_025220.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.693

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19849232).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.1583A>G	p.Gln528Arg	missense_variant	Exon 14 of 22	ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518.7	c.1583A>G	p.Gln528Arg	missense_variant	Exon 14 of 22	1	NM_025220.5	ENSP00000348912.3
ADAM33	ENST00000379861.8	c.1583A>G	p.Gln528Arg	missense_variant	Exon 14 of 22	1		ENSP00000369190.4
ADAM33	ENST00000466620.5	n.1222A>G		non_coding_transcript_exon_variant	Exon 4 of 11	1
ADAM33	ENST00000350009.6	c.1583A>G	p.Gln528Arg	missense_variant	Exon 14 of 21	5		ENSP00000322550.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.17	T;.;T;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.59
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.55	T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.;.;L
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.9	D;D;.;D
REVEL	Benign	0.036
Sift	Benign	0.080	T;T;.;T
Sift4G	Benign	0.37	T;T;T;T
Polyphen		0.050	B;B;.;B
Vest4		0.29
MutPred		0.41		Loss of disorder (P = 0.1185);Loss of disorder (P = 0.1185);.;Loss of disorder (P = 0.1185);
MVP		0.27
MPC		0.065
ClinPred		0.13	T
GERP RS		1.0
Varity_R		0.29
gMVP		0.70

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

Other links and lift over

dbSNP: rs776168462; hg19: chr20-3652795;