Genetic Variant ENTREP3:p.Arg650His (chr1-155247840-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006589.3(ENTREP3):c.1949G>A(p.Arg650His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000396 in 1,490,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

ENTREP3
NM_006589.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0610

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029114068).

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.1949G>A	p.Arg650His	missense	Exon 12 of 12	NP_006580.2
ENTREP3	NM_001267608.2		c.1895G>A	p.Arg632His	missense	Exon 11 of 11	NP_001254537.1	P81408-3
ENTREP3	NM_198264.2		c.1661G>A	p.Arg554His	missense	Exon 9 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.1949G>A	p.Arg650His	missense	Exon 12 of 12	ENSP00000354958.2	P81408-1
ENTREP3	ENST00000368368.7	TSL:1	c.1895G>A	p.Arg632His	missense	Exon 11 of 11	ENSP00000357352.3	P81408-3
ENTREP3	ENST00000350210.6	TSL:1	c.1661G>A	p.Arg554His	missense	Exon 9 of 9	ENSP00000307128.4	P81408-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000184

AC:

AN:

108686

AF XY:

0.0000180

show subpopulations

Gnomad AFR exome

AF:

0.000113

Gnomad AMR exome

AF:

0.0000651

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

AF:

0.0000411

AC:

AN:

1338416

Hom.:

Cov.:

AF XY:

0.0000443

AC XY:

AN XY:

654036

show subpopulations

African (AFR)

AF:

0.0000336

AC:

AN:

29758

American (AMR)

AF:

0.0000804

AC:

AN:

24864

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20184

East Asian (EAS)

AF:

0.00

AC:

AN:

36590

South Asian (SAS)

AF:

0.0000441

AC:

AN:

68002

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46894

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4842

European-Non Finnish (NFE)

AF:

0.0000456

AC:

AN:

1052100

Other (OTH)

AF:

0.0000181

AC:

AN:

55182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41460

American (AMR)

AF:

0.0000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000325

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000171

AC:

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

0.076

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.65

CADD

Benign

8.3

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0098

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.069

M_CAP

Benign

0.0057

MetaRNN

Benign

0.029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

-0.061

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.72

REVEL

Benign

0.022

Sift

Benign

0.26

Sift4G

Benign

0.14

Polyphen

0.0050

Vest4

0.087

MutPred

0.20

Loss of MoRF binding (P = 0.0236)

MVP

0.14

MPC

0.10

ClinPred

0.038

GERP RS

1.6

Varity_R

0.027

gMVP

0.30

Mutation Taster

=98/2

polymorphism

(source)

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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over