Genetic Variant NM_006589.3:c.1427G>A (chr1-155250359-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006589.3(ENTREP3):c.1427G>A(p.Arg476Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ENTREP3
NM_006589.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.599

Publications

0 publications found

Variant links:

Genes affected

ENTREP3 (HGNC:1233): (endosomal transmembrane epsin interactor 3) This gene is located near the gene for the lysosomal enzyme glucosylceramidase; a deficiency in this enzyme is associated with Gaucher disease. The encoded protein has been identified as a potential binding partner of a WW domain-containing protein which is involved in apoptosis and tumor suppression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

ENTREP3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09893739).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006589.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENTREP3	NM_006589.3	MANE Select	c.1427G>A	p.Arg476Gln	missense	Exon 9 of 12	NP_006580.2
ENTREP3	NM_001267608.2		c.1373G>A	p.Arg458Gln	missense	Exon 8 of 11	NP_001254537.1	P81408-3
ENTREP3	NM_198264.2		c.1139G>A	p.Arg380Gln	missense	Exon 6 of 9	NP_937995.1	P81408-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENTREP3	ENST00000361361.7	TSL:1 MANE Select	c.1427G>A	p.Arg476Gln	missense	Exon 9 of 12	ENSP00000354958.2	P81408-1
ENTREP3	ENST00000368368.7	TSL:1	c.1373G>A	p.Arg458Gln	missense	Exon 8 of 11	ENSP00000357352.3	P81408-3
ENTREP3	ENST00000350210.6	TSL:1	c.1139G>A	p.Arg380Gln	missense	Exon 6 of 9	ENSP00000307128.4	P81408-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

144410

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1154596

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

566294

African (AFR)

AF:

0.00

AC:

AN:

24086

American (AMR)

AF:

0.00

AC:

AN:

28154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15994

East Asian (EAS)

AF:

0.00

AC:

AN:

12768

South Asian (SAS)

AF:

0.00

AC:

AN:

76728

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28512

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2838

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

923818

Other (OTH)

AF:

0.00

AC:

AN:

41698

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0021

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.52

M_CAP

Benign

0.0088

MetaRNN

Benign

0.099

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.20

PhyloP100

0.60

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.10

REVEL

Benign

0.048

Sift

Benign

0.28

Sift4G

Benign

0.13

Polyphen

0.048

Vest4

0.23

MutPred

0.17

Loss of methylation at R476 (P = 0.048)

MVP

0.18

MPC

1.7

ClinPred

0.27

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.039

gMVP

0.23

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over