Genetic Variant ADRM1:p.Pro315Pro (chr20-62308109-A-G) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_007002.4(ADRM1):c.945A>G(p.Pro315Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000631 in 1,611,298 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 2 hom., cov: 34)

Exomes 𝑓: 0.00031 ( 2 hom. )

Consequence

ADRM1
NM_007002.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.156

Publications

2 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:

LAMA5 (HGNC:6485): (laminin subunit alpha 5) This gene encodes one of the vertebrate laminin alpha chains. Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. The protein encoded by this gene is the alpha-5 subunit of of laminin-10 (laminin-511), laminin-11 (laminin-521) and laminin-15 (laminin-523). [provided by RefSeq, Jun 2013]

LAMA5 Gene-Disease associations (from GenCC):

LAMA5-related multisystemic syndrome
Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
nephrotic syndrome, IIa 26
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

LAMA5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 20-62308109-A-G is Benign according to our data. Variant chr20-62308109-A-G is described in ClinVar as Benign. ClinVar VariationId is 787497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.156 with no splicing effect.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADRM1	NM_007002.4	MANE Select	c.945A>G	p.Pro315Pro	synonymous	Exon 8 of 10	NP_008933.2
ADRM1	NM_175573.2		c.945A>G	p.Pro315Pro	synonymous	Exon 8 of 10	NP_783163.1	Q16186
ADRM1	NM_001281437.1		c.828A>G	p.Pro276Pro	synonymous	Exon 7 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.945A>G	p.Pro315Pro	synonymous	Exon 8 of 10	ENSP00000253003.2	Q16186
ADRM1	ENST00000906321.1		c.945A>G	p.Pro315Pro	synonymous	Exon 8 of 10	ENSP00000576380.1
ADRM1	ENST00000906322.1		c.996A>G	p.Pro332Pro	synonymous	Exon 8 of 10	ENSP00000576381.1

Frequencies

GnomAD3 genomes

AF:

0.00367

AC:

558

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.000829

AC:

205

AN:

247390

AF XY:

0.000573

show subpopulations

Gnomad AFR exome

AF:

0.0121

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000893

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000315

AC:

459

AN:

1458996

Hom.:

Cov.:

AF XY:

0.000267

AC XY:

194

AN XY:

725798

show subpopulations

African (AFR)

AF:

0.0122

AC:

408

AN:

33478

American (AMR)

AF:

0.000336

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50884

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111834

Other (OTH)

AF:

0.000497

AC:

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

104

139

174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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

AF:

0.00366

AC:

557

AN:

152302

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

274

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0129

AC:

537

AN:

41566

American (AMR)

AF:

0.000915

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

109

136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00169

Hom.:

Bravo

AF:

0.00399

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.4

(source)

DANN

Benign

0.69

PhyloP100

-0.16

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over