Variant 20-62308135-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_007002.4(ADRM1):c.971C>T(p.Ala324Val) variant causes a missense change. The variant allele was found at a frequency of 0.012 in 1,609,056 control chromosomes in the GnomAD database, including 140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0087 ( 11 hom., cov: 34)

Exomes 𝑓: 0.012 ( 129 hom. )

Consequence

ADRM1
NM_007002.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.73

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:):

LAMA5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008605361).

BP6

Variant 20-62308135-C-T is Benign according to our data. Variant chr20-62308135-C-T is described in ClinVar as [Benign]. Clinvar id is 790289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62308135-C-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRM1	NM_007002.4 linkuse as main transcript	c.971C>T	p.Ala324Val	missense_variant	8/10	ENST00000253003.7	NP_008933.2	Q16186

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADRM1	ENST00000253003.7 linkuse as main transcript	c.971C>T	p.Ala324Val	missense_variant	8/10	1	NM_007002.4	ENSP00000253003.2	Q16186
ADRM1	ENST00000491935.5 linkuse as main transcript	c.971C>T	p.Ala324Val	missense_variant	9/11	5		ENSP00000478877.1	Q16186
ADRM1	ENST00000620230.4 linkuse as main transcript	c.854C>T	p.Ala285Val	missense_variant	7/9	5		ENSP00000480756.1	A0A087WX59
LAMA5	ENST00000492698.1 linkuse as main transcript	n.714G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.00874

AC:

1330

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00260

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00962

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00580

Gnomad FIN

AF:

0.00329

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0146

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00822

AC:

2017

AN:

245264

Hom.:

AF XY:

0.00844

AC XY:

1126

AN XY:

133404

show subpopulations

Gnomad AFR exome

AF:

0.00125

Gnomad AMR exome

AF:

0.00583

Gnomad ASJ exome

AF:

0.000402

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00706

Gnomad FIN exome

AF:

0.00294

Gnomad NFE exome

AF:

0.0131

Gnomad OTH exome

AF:

0.00930

GnomAD4 exome

AF:

0.0123

AC:

17903

AN:

1456714

Hom.:

129

Cov.:

AF XY:

0.0122

AC XY:

8820

AN XY:

724692

show subpopulations

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.00618

Gnomad4 ASJ exome

AF:

0.000804

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00783

Gnomad4 FIN exome

AF:

0.00396

Gnomad4 NFE exome

AF:

0.0144

Gnomad4 OTH exome

AF:

0.0113

GnomAD4 genome

AF:

0.00872

AC:

1328

AN:

152342

Hom.:

Cov.:

AF XY:

0.00797

AC XY:

594

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00260

Gnomad4 AMR

AF:

0.00961

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00559

Gnomad4 FIN

AF:

0.00329

Gnomad4 NFE

AF:

0.0146

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.0121

Hom.:

Bravo

AF:

0.00858

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0127

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0132

AC:

113

ExAC

AF:

0.00822

AC:

992

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.0133

EpiControl

AF:

0.0125

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

.;D;D

MetaRNN

Benign

0.0086

T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.3

M;.;M

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.7

.;.;N

REVEL

Benign

0.25

Sift

Benign

0.10

.;.;T

Sift4G

Benign

0.23

T;T;T

Polyphen

0.99

D;.;D

Vest4

0.41

MVP

0.43

MPC

0.11

ClinPred

0.034

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.40

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over