chr1-155247900-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006589.3(ENTREP3):​c.1889G>T​(p.Cys630Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000271 in 1,583,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ENTREP3
NM_006589.3 missense

Scores

1
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.52
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.41614512).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ENTREP3NM_006589.3 linkc.1889G>T p.Cys630Phe missense_variant Exon 12 of 12 ENST00000361361.7 NP_006580.2 P81408-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ENTREP3ENST00000361361.7 linkc.1889G>T p.Cys630Phe missense_variant Exon 12 of 12 1 NM_006589.3 ENSP00000354958.2 P81408-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152244
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
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:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000514
AC:
11
AN:
214150
Hom.:
0
AF XY:
0.0000603
AC XY:
7
AN XY:
116182
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000335
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:
0.0000937
Gnomad OTH exome
AF:
0.000192
GnomAD4 exome
AF:
0.0000251
AC:
36
AN:
1431728
Hom.:
0
Cov.:
33
AF XY:
0.0000394
AC XY:
28
AN XY:
709854
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000502
Gnomad4 ASJ exome
AF:
0.0000412
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000282
Gnomad4 OTH exome
AF:
0.0000339
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152244
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.0000482
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:
0.0000735
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000378
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 22, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1889G>T (p.C630F) alteration is located in exon 12 (coding exon 12) of the FAM189B gene. This alteration results from a G to T substitution at nucleotide position 1889, causing the cysteine (C) at amino acid position 630 to be replaced by a phenylalanine (F). 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
0.88
BayesDel_addAF
Uncertain
0.017
T
BayesDel_noAF
Uncertain
-0.010
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.25
.;.;T
Eigen
Benign
0.15
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Uncertain
0.94
D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.42
T;T;T
MetaSVM
Benign
-0.79
T
MutationAssessor
Benign
1.1
.;.;L
PrimateAI
Uncertain
0.77
T
PROVEAN
Uncertain
-3.7
D;D;D
REVEL
Benign
0.21
Sift
Uncertain
0.0010
D;D;D
Sift4G
Uncertain
0.0020
D;D;D
Polyphen
0.51
P;.;B
Vest4
0.68
MutPred
0.47
.;.;Gain of MoRF binding (P = 0.0707);
MVP
0.27
MPC
0.21
ClinPred
0.69
D
GERP RS
4.5
Varity_R
0.71
gMVP
0.52

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.

Other links and lift over

dbSNP: rs750576160; hg19: chr1-155217691; API