dbSNP rs780960999: ADRM1:p.Ala239Thr (chr20-62307687-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007002.4(ADRM1):c.715G>A(p.Ala239Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,459,958 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.71

Publications

0 publications found

Variant links:

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]

ADRM1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.080734015).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADRM1	NM_007002.4	MANE Select	c.715G>A	p.Ala239Thr	missense	Exon 7 of 10	NP_008933.2
ADRM1	NM_175573.2		c.715G>A	p.Ala239Thr	missense	Exon 7 of 10	NP_783163.1	Q16186
ADRM1	NM_001281437.1		c.598G>A	p.Ala200Thr	missense	Exon 6 of 9	NP_001268366.1	Q16186

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADRM1	ENST00000253003.7	TSL:1 MANE Select	c.715G>A	p.Ala239Thr	missense	Exon 7 of 10	ENSP00000253003.2	Q16186
ADRM1	ENST00000906321.1		c.715G>A	p.Ala239Thr	missense	Exon 7 of 10	ENSP00000576380.1
ADRM1	ENST00000906322.1		c.766G>A	p.Ala256Thr	missense	Exon 7 of 10	ENSP00000576381.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000203

AC:

AN:

246374

AF XY:

0.0000224

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000907

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1459958

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726310

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.0000895

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51750

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111866

Other (OTH)

AF:

0.00

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000829

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.069

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.75

M_CAP

Benign

0.012

MetaRNN

Benign

0.081

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

4.7

PrimateAI

Benign

0.38

PROVEAN

Benign

0.27

REVEL

Benign

0.045

Sift

Benign

0.57

Sift4G

Benign

0.44

Polyphen

0.0

Vest4

0.11

MutPred

0.36

Gain of glycosylation at A239 (P = 3e-04)

MVP

0.24

MPC

0.11

ClinPred

0.28

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.049

gMVP

0.39

Mutation Taster

=81/19

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over