20-62307625-C-A

Position:

• chr20-62307625-C-A

Variant summary

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

The ENST00000253003.7(ADRM1):​c.653C>A​(p.Pro218Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ADRM1 ENST00000253003.7 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 6.24

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]

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
ADRM1	NM_007002.4	c.653C>A	p.Pro218Gln	missense_variant	7/10	ENST00000253003.7	NP_008933.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRM1	ENST00000253003.7	c.653C>A	p.Pro218Gln	missense_variant	7/10	1	NM_007002.4	ENSP00000253003	P1
ADRM1	ENST00000491935.5	c.653C>A	p.Pro218Gln	missense_variant	8/11	5		ENSP00000478877	P1
ADRM1	ENST00000620230.4	c.536C>A	p.Pro179Gln	missense_variant	6/9	5		ENSP00000480756

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.0016	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.11	T;.;T
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.91	.;D;D
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.62	D;D;D
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.8	L;.;L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.7	.;.;N
REVEL	Benign	0.21
Sift	Benign	0.12	.;.;T
Sift4G	Benign	0.29	T;T;T
Polyphen		0.98	D;.;D
Vest4		0.58
MutPred		0.53		Loss of glycosylation at P218 (P = 0.018);.;Loss of glycosylation at P218 (P = 0.018);
MVP		0.39
MPC		0.10
ClinPred		0.83	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs193921052; hg19: chr20-60882681; COSMIC: COSV53367625; COSMIC: COSV53367625;