20-62303667-G-C

Variant names:

• chr20-62303667-G-C
• NM_007002.4:c.99G>C
• ADRM1 p.Leu33Leu

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_007002.4(ADRM1):​c.99G>C​(p.Leu33Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ADRM1 NM_007002.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=0.006 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007002.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRM1	NM_007002.4	MANE Select	c.99G>C	p.Leu33Leu	synonymous	Exon 2 of 10	NP_008933.2
	ADRM1	NM_175573.2		c.99G>C	p.Leu33Leu	synonymous	Exon 2 of 10	NP_783163.1	Q16186
	ADRM1	NM_001281437.1		c.99G>C	p.Leu33Leu	synonymous	Exon 2 of 9	NP_001268366.1	Q16186

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRM1	ENST00000253003.7	TSL:1 MANE Select	c.99G>C	p.Leu33Leu	synonymous	Exon 2 of 10	ENSP00000253003.2	Q16186
	ADRM1	ENST00000906321.1		c.99G>C	p.Leu33Leu	synonymous	Exon 2 of 10	ENSP00000576380.1
	ADRM1	ENST00000906322.1		c.99G>C	p.Leu33Leu	synonymous	Exon 2 of 10	ENSP00000576381.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.4
DANN	Benign	0.80
PhyloP100		0.0060
PromoterAI		0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-60878723;