rs745350807

Variant names:

• chr20-3672159-C-A
• rs745350807
• NM_025220.5:c.1572G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-3672159-C-A
• chr20-3672159-C-G

Variant summary

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

The NM_025220.5(ADAM33):​c.1572G>T​(p.Gln524His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 1.70

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;.;T;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.68	T;T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.;.;L
PrimateAI	Benign	0.38	T
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		0.99	D
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

Other links and lift over

dbSNP: rs745350807; hg19: chr20-3652806;