chr20-62308736-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_007002.4(ADRM1):c.1199A>G(p.Glu400Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,612,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
ADRM1
NM_007002.4 missense
NM_007002.4 missense
Scores
1
5
8
Clinical Significance
Conservation
PhyloP100: 6.98
Genes affected
ADRM1 (HGNC:15759): (ADRM1 26S proteasome ubiquitin receptor) This gene encodes a member of the adhesion regulating molecule 1 protein family. The encoded protein is a component of the proteasome where it acts as a ubiquitin receptor and recruits the deubiquitinating enzyme, ubiquitin carboxyl-terminal hydrolase L5. Increased levels of the encoded protein are associated with increased cell adhesion, which is likely an indirect effect of this intracellular protein. Dysregulation of this gene has been implicated in carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
LAMA5 (HGNC:6485): (laminin subunit alpha 5) This gene encodes one of the vertebrate laminin alpha chains. Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. The protein encoded by this gene is the alpha-5 subunit of of laminin-10 (laminin-511), laminin-11 (laminin-521) and laminin-15 (laminin-523). [provided by RefSeq, Jun 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.32262284).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADRM1 | NM_007002.4 | c.1199A>G | p.Glu400Gly | missense_variant | 10/10 | ENST00000253003.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADRM1 | ENST00000253003.7 | c.1199A>G | p.Glu400Gly | missense_variant | 10/10 | 1 | NM_007002.4 | P1 | |
ADRM1 | ENST00000491935.5 | c.1199A>G | p.Glu400Gly | missense_variant | 11/11 | 5 | P1 | ||
ADRM1 | ENST00000620230.4 | c.1082A>G | p.Glu361Gly | missense_variant | 9/9 | 5 | |||
LAMA5 | ENST00000492698.1 | n.402+120T>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152240Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249546Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135442
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460690Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726620
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152240Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74388
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 07, 2022 | The c.1199A>G (p.E400G) alteration is located in exon 10 (coding exon 9) of the ADRM1 gene. This alteration results from a A to G substitution at nucleotide position 1199, causing the glutamic acid (E) at amino acid position 400 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Pathogenic
DEOGEN2
Benign
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Benign
T
Sift4G
Uncertain
D;D;D
Polyphen
P;.;P
Vest4
MutPred
Gain of ubiquitination at K397 (P = 0.0477);.;Gain of ubiquitination at K397 (P = 0.0477);
MVP
MPC
0.13
ClinPred
D
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