14-70523137-A-C

Position:

• chr14-70523137-A-C

Variant summary

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

The NM_003814.5(ADAM20):​c.1621T>G​(p.Phe541Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAM20 NM_003814.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.62

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]

ENSG00000257759 (HGNC:):

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/exons	MANE	Protein	UniProt
ADAM20	NM_003814.5	c.1621T>G	p.Phe541Val	missense_variant	2/2	ENST00000256389.5	NP_003805.4
ADAM20	XM_005268151.4	c.1771T>G	p.Phe591Val	missense_variant	2/2		XP_005268208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM20	ENST00000256389.5	c.1621T>G	p.Phe541Val	missense_variant	2/2	1	NM_003814.5	ENSP00000256389.3
ADAM20	ENST00000652041.1	c.1771T>G	p.Phe591Val	missense_variant	2/2			ENSP00000498512.1
ENSG00000257759	ENST00000556646.1	n.183+24145T>G		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.1771T>G (p.F591V) alteration is located in exon 2 (coding exon 1) of the ADAM20 gene. This alteration results from a T to G substitution at nucleotide position 1771, causing the phenylalanine (F) at amino acid position 591 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.69	T
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.32
Sift	Benign	0.068	T
Sift4G	Uncertain	0.046	D
Vest4		0.65
MVP		0.44
MPC		0.24
ClinPred		0.98	D
GERP RS		4.7

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-70989854;