Variant chr22-23838591-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001002862.3(DERL3):c.206T>G(p.Phe69Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000367 in 1,578,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

DERL3
NM_001002862.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.03

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.879

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DERL3	NM_001002862.3 linkuse as main transcript	c.206T>G	p.Phe69Cys	missense_variant	3/7	ENST00000318109.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DERL3	ENST00000318109.12 linkuse as main transcript	c.206T>G	p.Phe69Cys	missense_variant	3/7	1	NM_001002862.3	P1	Q96Q80-1

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

148740

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000473

AC:

AN:

211608

Hom.:

AF XY:

0.00000874

AC XY:

AN XY:

114364

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:

0.0000107

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000392

AC:

AN:

1429786

Hom.:

Cov.:

AF XY:

0.0000409

AC XY:

AN XY:

709450

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000475

Gnomad4 OTH exome

AF:

0.0000680

GnomAD4 genome

AF:

0.0000134

AC:

AN:

148740

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

72500

show subpopulations

Gnomad4 AFR

AF:

0.0000245

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:

0.0000149

Gnomad4 OTH

AF:

0.00

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.00000829

AC:

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

Jun 17, 2022

The c.206T>G (p.F69C) alteration is located in exon 3 (coding exon 3) of the DERL3 gene. This alteration results from a T to G substitution at nucleotide position 206, causing the phenylalanine (F) at amino acid position 69 to be replaced by a cysteine (C). 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

Pathogenic

0.83

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

.;T;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.98

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.88

D;D;D

MetaSVM

Uncertain

0.31

MutationAssessor

Pathogenic

3.9

H;H;H

MutationTaster

Benign

1.0

D;D;D;N

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-6.5

D;D;D

REVEL

Uncertain

0.53

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.90

MutPred

0.58

Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);

MVP

0.64

MPC

0.65

ClinPred

1.0

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.93

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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