Variant 22-23837147-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001002862.3(DERL3):c.531G>A(p.Ala177=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,613,928 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 9 hom. )

Consequence

DERL3
NM_001002862.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.84

Variant links:

Genes affected

DERL3 (HGNC:14236): (derlin 3) The protein encoded by this gene belongs to the derlin family, and resides in the endoplasmic reticulum (ER). Proteins that are unfolded or misfolded in the ER must be refolded or degraded to maintain the homeostasis of the ER. This protein appears to be involved in the degradation of misfolded glycoproteins in the ER. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Oct 2008]

DERL3 links:

SMARCB1 (HGNC:11103): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1) The protein encoded by this gene is part of a complex that relieves repressive chromatin structures, allowing the transcriptional machinery to access its targets more effectively. The encoded nuclear protein may also bind to and enhance the DNA joining activity of HIV-1 integrase. This gene has been found to be a tumor suppressor, and mutations in it have been associated with malignant rhabdoid tumors. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

SMARCB1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 22-23837147-C-T is Benign according to our data. Variant chr22-23837147-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1298887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.84 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DERL3	NM_001002862.3 linkuse as main transcript	c.531G>A	p.Ala177=	synonymous_variant	6/7	ENST00000318109.12
SMARCB1	NM_003073.5 linkuse as main transcript	c.*2967C>T		3_prime_UTR_variant	9/9	ENST00000644036.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DERL3	ENST00000318109.12 linkuse as main transcript	c.531G>A	p.Ala177=	synonymous_variant	6/7	1	NM_001002862.3	P1	Q96Q80-1
SMARCB1	ENST00000644036.2 linkuse as main transcript	c.*2967C>T		3_prime_UTR_variant	9/9		NM_003073.5	A1	Q12824-1

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

215

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00234

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00173

AC:

433

AN:

250252

Hom.:

AF XY:

0.00185

AC XY:

251

AN XY:

135564

show subpopulations

Gnomad AFR exome

AF:

0.000371

Gnomad AMR exome

AF:

0.000812

Gnomad ASJ exome

AF:

0.0000999

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.000832

Gnomad NFE exome

AF:

0.00288

Gnomad OTH exome

AF:

0.00328

GnomAD4 exome

AF:

0.00245

AC:

3580

AN:

1461636

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

1746

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00106

Gnomad4 FIN exome

AF:

0.000693

Gnomad4 NFE exome

AF:

0.00287

Gnomad4 OTH exome

AF:

0.00335

GnomAD4 genome

AF:

0.00141

AC:

215

AN:

152292

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00234

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00234

Hom.:

Bravo

AF:

0.00158

EpiCase

AF:

0.00240

EpiControl

AF:

0.00255

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

DERL3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

8.9

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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