chr20-3671907-C-G

Variant names:

• chr20-3671907-C-G
• rs765009386
• NM_025220.5:c.1676G>C

Variant summary

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

The NM_025220.5(ADAM33):​c.1676G>C​(p.Ser559Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: ADAM33 NM_025220.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.366

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=0.08964613).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.1676G>C	p.Ser559Thr	missense_variant	Exon 15 of 22	ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518.7	c.1676G>C	p.Ser559Thr	missense_variant	Exon 15 of 22	1	NM_025220.5	ENSP00000348912.3
ADAM33	ENST00000379861.8	c.1676G>C	p.Ser559Thr	missense_variant	Exon 15 of 22	1		ENSP00000369190.4
ADAM33	ENST00000466620.5	n.1315G>C		non_coding_transcript_exon_variant	Exon 5 of 11	1
ADAM33	ENST00000350009.6	c.1676G>C	p.Ser559Thr	missense_variant	Exon 15 of 21	5		ENSP00000322550.5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152248 Hom.: 0 Cov.: 33

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

GnomAD4 exome Cov.: 35

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152248 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74392

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

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.81
DEOGEN2	Benign	0.063	T;.;T;.
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.089	T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.090	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L;.;.;L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.7	N;N;.;N
REVEL	Benign	0.15
Sift	Benign	0.58	T;T;.;T
Sift4G	Benign	0.79	T;T;T;T
Polyphen		0.85	P;P;.;P
Vest4		0.11
MutPred		0.54		Loss of disorder (P = 0.0565);Loss of disorder (P = 0.0565);.;Loss of disorder (P = 0.0565);
MVP		0.36
MPC		0.061
ClinPred		0.14	T
GERP RS		-1.6
Varity_R		0.14
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs765009386; hg19: chr20-3652554;