14-70523285-CAC-TAA

Variant names:

• chr14-70523285-CAC-TAA
• NM_003814.5:c.1471_1473delGTGinsTTA
• ADAM20 p.Val491Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_003814.5(ADAM20):​c.1471_1473delGTGinsTTA​(p.Val491Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAM20 NM_003814.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 0 publications found

Genes affected

ADAM20 (HGNC:199): (ADAM metallopeptidase domain 20) 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. The expression of this gene is testis-specific. [provided by RefSeq, Jul 2008]

ADAM20 Gene-Disease associations (from GenCC):

• male infertility

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000257759 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003814.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM20	NM_003814.5	MANE Select	c.1471_1473delGTGinsTTA	p.Val491Leu	missense	N/A	NP_003805.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM20	ENST00000256389.5	TSL:1 MANE Select	c.1471_1473delGTGinsTTA	p.Val491Leu	missense	N/A	ENSP00000256389.3	O43506
	ADAM20	ENST00000652041.1		c.1621_1623delGTGinsTTA	p.Val541Leu	missense	N/A	ENSP00000498512.1	A0A494C0E3
	ENSG00000257759	ENST00000556646.1	TSL:4	n.183+23995_183+23997delGTGinsTTA		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-70990002;