chr20-62303727-C-G

Variant names:

• chr20-62303727-C-G
• rs115562292
• NM_007002.4:c.159C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_007002.4(ADRM1):​c.159C>G​(p.Asp53Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000501 in 1,612,366 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00028 (1 hom.)
• Consequence: ADRM1 NM_007002.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.165
• Publications: 2 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0123568475).
• BP6: Variant 20-62303727-C-G is Benign according to our data. Variant chr20-62303727-C-G is described in ClinVar as Benign. ClinVar VariationId is 722428.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.159C>G	p.Asp53Glu	missense	Exon 2 of 10	NP_008933.2
	ADRM1	NM_175573.2		c.159C>G	p.Asp53Glu	missense	Exon 2 of 10	NP_783163.1	Q16186
	ADRM1	NM_001281437.1		c.159C>G	p.Asp53Glu	missense	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.159C>G	p.Asp53Glu	missense	Exon 2 of 10	ENSP00000253003.2	Q16186
	ADRM1	ENST00000906321.1		c.159C>G	p.Asp53Glu	missense	Exon 2 of 10	ENSP00000576380.1
	ADRM1	ENST00000906322.1		c.159C>G	p.Asp53Glu	missense	Exon 2 of 10	ENSP00000576381.1

Frequencies

GnomAD3 genomes AF: 0.00262 AC: 398 AN: 152172 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00912

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00336

GnomAD2 exomes AF: 0.000773 AC: 193 AN: 249810 AF XY: 0.000472

Gnomad AFR exome AF: 0.0110

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000279 AC: 408 AN: 1460076 Hom.: 1 Cov.: 31 AF XY: 0.000234 AC XY: 170 AN XY: 726286

African (AFR) AF: 0.0101 AC: 338 AN: 33478

American (AMR) AF: 0.000492 AC: 22 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51708

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111944

Other (OTH) AF: 0.000696 AC: 42 AN: 60368

GnomAD4 genome AF: 0.00262 AC: 399 AN: 152290 Hom.: 2 Cov.: 33 AF XY: 0.00234 AC XY: 174 AN XY: 74466

African (AFR) AF: 0.00912 AC: 379 AN: 41558

American (AMR) AF: 0.000719 AC: 11 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00332 AC: 7 AN: 2108

Alfa AF: 0.000171 Hom.: 0

Bravo AF: 0.00322

ESP6500AA AF: 0.00908 AC: 40

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00101 AC: 122

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.58	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.095	N
PhyloP100		-0.17
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.075
Sift	Benign	0.34	T
Sift4G	Benign	0.38	T
Polyphen		0.14	B
Vest4		0.44
MutPred		0.66		Loss of catalytic residue at D53 (P = 0.1212)
MVP		0.34
MPC		1.3
ClinPred		0.019	T
GERP RS		-0.59
PromoterAI		-0.019	Neutral
Varity_R		0.33
gMVP		0.42
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs115562292; hg19: chr20-60878783;