20-62307702-C-T

Variant names:

• chr20-62307702-C-T
• rs770895009
• NM_007002.4:c.730C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_007002.4(ADRM1):​c.730C>T​(p.Pro244Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,459,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: ADRM1 NM_007002.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.41
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08356702).

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.730C>T	p.Pro244Ser	missense	Exon 7 of 10	NP_008933.2
	ADRM1	NM_175573.2		c.730C>T	p.Pro244Ser	missense	Exon 7 of 10	NP_783163.1	Q16186
	ADRM1	NM_001281437.1		c.613C>T	p.Pro205Ser	missense	Exon 6 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.730C>T	p.Pro244Ser	missense	Exon 7 of 10	ENSP00000253003.2	Q16186
	ADRM1	ENST00000906321.1		c.730C>T	p.Pro244Ser	missense	Exon 7 of 10	ENSP00000576380.1
	ADRM1	ENST00000906322.1		c.781C>T	p.Pro261Ser	missense	Exon 7 of 10	ENSP00000576381.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000367 AC: 9 AN: 245218 AF XY: 0.0000449

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000492

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1459908 Hom.: 0 Cov.: 33 AF XY: 0.00000826 AC XY: 6 AN XY: 726272

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111834

Other (OTH) AF: 0.00 AC: 0 AN: 60338

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000332 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Benign	0.89
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.052
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.90	L
PhyloP100		3.4
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.11
Sift	Benign	0.39	T
Sift4G	Benign	0.71	T
Polyphen		0.0010	B
Vest4		0.37
MutPred		0.31		Gain of phosphorylation at P244 (P = 0.0054)
MVP		0.19
MPC		0.11
ClinPred		0.094	T
GERP RS		5.3
Varity_R		0.11
gMVP		0.51
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs770895009; hg19: chr20-60882758;