20-3668784-A-T

Variant names:

• chr20-3668784-A-T
• rs677044
• ENST00000466620.5:n.2182T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000466620.5(ADAM33):​n.2182T>A variant causes a non coding transcript exon 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADAM33 ENST00000466620.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177
• Publications: 24 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.*179T>A		3_prime_UTR_variant	Exon 22 of 22	ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518.7	c.*179T>A		3_prime_UTR_variant	Exon 22 of 22	1	NM_025220.5	ENSP00000348912.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 562810 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 302438

African (AFR) AF: 0.00 AC: 0 AN: 16000

American (AMR) AF: 0.00 AC: 0 AN: 34756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16742

East Asian (EAS) AF: 0.00 AC: 0 AN: 34192

South Asian (SAS) AF: 0.00 AC: 0 AN: 58612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34810

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2212

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 335436

Other (OTH) AF: 0.00 AC: 0 AN: 30050

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 10043

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.57
PhyloP100		-0.18

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

Other links and lift over

dbSNP: rs677044; hg19: chr20-3649431;