15-58665141-T-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_001110.4(ADAM10):c.541A>G(p.Arg181Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000121 in 1,613,430 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as risk factor (no stars).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 1 hom. )
Consequence
ADAM10
NM_001110.4 missense
NM_001110.4 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 3.87
Genes affected
ADAM10 (HGNC:188): (ADAM metallopeptidase domain 10) Members of the ADAM family are cell surface proteins with a unique structure possessing both potential adhesion and protease domains. This gene encodes and ADAM family member that cleaves many proteins including TNF-alpha and E-cadherin. Alternate splicing results in multiple transcript variants encoding different proteins that may undergo similar processing. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, ADAM10
BS2
?
High AC in GnomAd at 27 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAM10 | NM_001110.4 | c.541A>G | p.Arg181Gly | missense_variant | 5/16 | ENST00000260408.8 | |
ADAM10 | NM_001320570.2 | c.541A>G | p.Arg181Gly | missense_variant | 5/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAM10 | ENST00000260408.8 | c.541A>G | p.Arg181Gly | missense_variant | 5/16 | 1 | NM_001110.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000177 AC: 27AN: 152174Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000167 AC: 42AN: 251260Hom.: 1 AF XY: 0.000199 AC XY: 27AN XY: 135804
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GnomAD4 exome AF: 0.000116 AC: 169AN: 1461256Hom.: 1 Cov.: 30 AF XY: 0.000116 AC XY: 84AN XY: 726972
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GnomAD4 genome ? AF: 0.000177 AC: 27AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.000256 AC XY: 19AN XY: 74360
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ClinVar
Significance: risk factor
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Alzheimer disease 18 Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Oct 16, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at