20-62307770-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_007002.4(ADRM1):c.798C>T(p.Asp266=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 1,611,772 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00020 (2 hom.)
• Consequence: ADRM1 NM_007002.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.56

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

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 20-62307770-C-T is Benign according to our data. Variant chr20-62307770-C-T is described in ClinVar as [Benign]. Clinvar id is 777607.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.56 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRM1	NM_007002.4	c.798C>T	p.Asp266=	synonymous_variant	7/10	ENST00000253003.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRM1	ENST00000253003.7	c.798C>T	p.Asp266=	synonymous_variant	7/10	1	NM_007002.4	P1
ADRM1	ENST00000491935.5	c.798C>T	p.Asp266=	synonymous_variant	8/11	5		P1
ADRM1	ENST00000620230.4	c.681C>T	p.Asp227=	synonymous_variant	6/9	5

Frequencies

GnomAD3 genomes AF: 0.00130 AC: 198 AN: 152236 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00398

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000527 AC: 127 AN: 240968 Hom.: 1 AF XY: 0.000418 AC XY: 55 AN XY: 131682

Gnomad AFR exome AF: 0.00419

Gnomad AMR exome AF: 0.000965

Gnomad ASJ exome AF: 0.00195

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000753

Gnomad OTH exome AF: 0.000510

GnomAD4 exome AF: 0.000204 AC: 297 AN: 1459418 Hom.: 2 Cov.: 33 AF XY: 0.000165 AC XY: 120 AN XY: 726006

Gnomad4 AFR exome AF: 0.00371

Gnomad4 AMR exome AF: 0.00101

Gnomad4 ASJ exome AF: 0.00180

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000387

Gnomad4 OTH exome AF: 0.000581

GnomAD4 genome AF: 0.00130 AC: 198 AN: 152354 Hom.: 0 Cov.: 34 AF XY: 0.00119 AC XY: 89 AN XY: 74512

Gnomad4 AFR AF: 0.00397

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000698 Hom.: 0

Bravo AF: 0.00149

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	7.6
Dann	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

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

Other links and lift over

dbSNP: rs139296980; hg19: chr20-60882826; COSMIC: COSV99440629; COSMIC: COSV99440629;