Variant 20-62308681-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007002.4(ADRM1):c.1144C>G(p.Gln382Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000241 in 1,612,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

ADRM1
NM_007002.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.65

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12484521).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRM1	NM_007002.4 linkuse as main transcript	c.1144C>G	p.Gln382Glu	missense_variant	10/10	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.1144C>G	p.Gln382Glu	missense_variant	10/10	1	NM_007002.4	ENSP00000253003.2	Q16186
ADRM1	ENST00000491935.5 linkuse as main transcript	c.1144C>G	p.Gln382Glu	missense_variant	11/11	5		ENSP00000478877.1	Q16186
ADRM1	ENST00000620230.4 linkuse as main transcript	c.1027C>G	p.Gln343Glu	missense_variant	9/9	5		ENSP00000480756.1	A0A087WX59
LAMA5	ENST00000492698.1 linkuse as main transcript	n.402+175G>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000921

AC:

AN:

249610

Hom.:

AF XY:

0.0000738

AC XY:

AN XY:

135456

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000196

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000255

AC:

372

AN:

1460728

Hom.:

Cov.:

AF XY:

0.000246

AC XY:

179

AN XY:

726636

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000326

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000112

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000301

Hom.:

Bravo

AF:

0.000151

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 05, 2024

The c.1144C>G (p.Q382E) alteration is located in exon 10 (coding exon 9) of the ADRM1 gene. This alteration results from a C to G substitution at nucleotide position 1144, causing the glutamine (Q) at amino acid position 382 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.058

T;.;T

Eigen

Benign

-0.21

Eigen_PC

Benign

0.069

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.87

.;D;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.99

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.26

.;.;N

REVEL

Benign

0.12

Sift

Benign

0.93

.;.;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.12

B;.;B

Vest4

0.45

MVP

0.34

MPC

0.12

ClinPred

0.13

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.83

gMVP

0.16

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