Variant 22-23838723-G-C 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_001002862.3(DERL3):c.147C>G(p.Phe49Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000516 in 1,550,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

DERL3
NM_001002862.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.16

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:

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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=0.14182442).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DERL3	NM_001002862.3 linkuse as main transcript	c.147C>G	p.Phe49Leu	missense_variant	2/7	ENST00000318109.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DERL3	ENST00000318109.12 linkuse as main transcript	c.147C>G	p.Phe49Leu	missense_variant	2/7	1	NM_001002862.3	P1	Q96Q80-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000388

AC:

AN:

154714

Hom.:

AF XY:

0.0000488

AC XY:

AN XY:

81896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000532

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000501

AC:

AN:

1398462

Hom.:

Cov.:

AF XY:

0.00000870

AC XY:

AN XY:

689702

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000168

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

.;T;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.91

M_CAP

Benign

0.033

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.72

N;N;N

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.82

N;N;N

REVEL

Benign

0.042

Sift

Benign

0.40

T;T;T

Sift4G

Benign

0.25

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.31

MutPred

0.65

Loss of ubiquitination at K51 (P = 0.0768);Loss of ubiquitination at K51 (P = 0.0768);Loss of ubiquitination at K51 (P = 0.0768);

MVP

0.39

MPC

0.14

ClinPred

0.078

GERP RS

4.5

Varity_R

0.20

gMVP

0.78

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over