14-70523182-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003814.5(ADAM20):​c.1576G>A​(p.Ala526Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A526S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ADAM20
NM_003814.5 missense

Scores

5
6
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.74
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.747

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADAM20NM_003814.5 linkc.1576G>A p.Ala526Thr missense_variant Exon 2 of 2 ENST00000256389.5 NP_003805.4 O43506A0A494C0E3
ADAM20XM_005268151.4 linkc.1726G>A p.Ala576Thr missense_variant Exon 2 of 2 XP_005268208.1 O43506A0A494C0E3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADAM20ENST00000256389.5 linkc.1576G>A p.Ala526Thr missense_variant Exon 2 of 2 1 NM_003814.5 ENSP00000256389.3 O43506
ADAM20ENST00000652041.1 linkc.1726G>A p.Ala576Thr missense_variant Exon 2 of 2 ENSP00000498512.1 A0A494C0E3
ENSG00000257759ENST00000556646.1 linkn.183+24100G>A intron_variant Intron 1 of 2 4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250848
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135544
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461742
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.54
BayesDel_addAF
Benign
-0.028
T
BayesDel_noAF
Benign
-0.28
CADD
Uncertain
25
DANN
Pathogenic
1.0
Eigen
Pathogenic
0.78
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.024
T
MetaRNN
Pathogenic
0.75
D
MetaSVM
Uncertain
-0.24
T
PrimateAI
Benign
0.40
T
PROVEAN
Uncertain
-3.9
D
REVEL
Uncertain
0.31
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Vest4
0.59
MVP
0.62
MPC
0.23
ClinPred
1.0
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs150024122; hg19: chr14-70989899; API