1-155248303-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006589.3(ENTREP3):​c.1580G>T​(p.Gly527Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,607,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00069 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000087 ( 0 hom. )

Consequence

ENTREP3
NM_006589.3 missense, splice_region

Scores

1
5
12
Splicing: ADA: 0.9985
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ENTREP3NM_006589.3 linkc.1580G>T p.Gly527Val missense_variant, splice_region_variant Exon 11 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.1580G>T p.Gly527Val missense_variant, splice_region_variant Exon 11 of 12 1 NM_006589.3 ENSP00000354958.2 P81408-1

Frequencies

GnomAD3 genomes
AF:
0.000697
AC:
106
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00246
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
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:
0.000478
GnomAD3 exomes
AF:
0.000202
AC:
50
AN:
246918
Hom.:
0
AF XY:
0.000142
AC XY:
19
AN XY:
133462
show subpopulations
Gnomad AFR exome
AF:
0.00224
Gnomad AMR exome
AF:
0.000234
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000167
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.0000873
AC:
127
AN:
1455158
Hom.:
0
Cov.:
33
AF XY:
0.0000692
AC XY:
50
AN XY:
722892
show subpopulations
Gnomad4 AFR exome
AF:
0.00312
Gnomad4 AMR exome
AF:
0.000158
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000933
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
AF:
0.000689
AC:
105
AN:
152286
Hom.:
0
Cov.:
32
AF XY:
0.000524
AC XY:
39
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.00245
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000543
Hom.:
0
Bravo
AF:
0.000782
ESP6500AA
AF:
0.00295
AC:
13
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000214
AC:
26
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1580G>T (p.G527V) alteration is located in exon 11 (coding exon 11) of the FAM189B gene. This alteration results from a G to T substitution at nucleotide position 1580, causing the glycine (G) at amino acid position 527 to be replaced by a valine (V). 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
Benign
0.23
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0084
.;.;T;T
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Uncertain
0.85
D
M_CAP
Benign
0.0075
T
MetaRNN
Benign
0.012
T;T;T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
0.97
.;.;L;.
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-0.64
N;N;N;N
REVEL
Benign
0.15
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Benign
0.087
T;T;T;D
Polyphen
1.0
D;.;D;.
Vest4
0.79
MVP
0.29
MPC
0.51
ClinPred
0.11
T
GERP RS
4.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.22
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.86
SpliceAI score (max)
0.040
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: rs148662301; hg19: chr1-155218094; API