5-77077701-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032367.4(ZBED3):​c.178G>A​(p.Gly60Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000838 in 1,193,944 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: not found (cov: 32)
Exomes 𝑓: 8.4e-7 ( 0 hom. )

Consequence

ZBED3
NM_032367.4 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.194
Variant links:
Genes affected
ZBED3 (HGNC:20711): (zinc finger BED-type containing 3) This gene belongs to a class of genes that arose through hAT DNA transposition and that encode regulatory proteins. This gene is upregulated in lung cancer tissues, where the encoded protein causes an accumulation of beta-catenin and enhanced lung cancer cell invasion. In addition, the encoded protein can be secreted and be involved in resistance to insulin. [provided by RefSeq, Jul 2016]

Genome browser will be placed here

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=0.20041063).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZBED3NM_032367.4 linkc.178G>A p.Gly60Arg missense_variant Exon 3 of 3 ENST00000255198.3 NP_115743.1 Q96IU2
ZBED3NM_001329564.2 linkc.178G>A p.Gly60Arg missense_variant Exon 2 of 2 NP_001316493.1 Q96IU2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZBED3ENST00000255198.3 linkc.178G>A p.Gly60Arg missense_variant Exon 3 of 3 1 NM_032367.4 ENSP00000255198.2 Q96IU2
ENSG00000285000ENST00000646704.1 linkn.1809+15899C>T intron_variant Intron 13 of 15 ENSP00000495089.1 A0A2R8YFF1
ZBED3ENST00000511587.1 linkc.178G>A p.Gly60Arg missense_variant Exon 2 of 2 3 ENSP00000427487.1 D6RIC4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
8.38e-7
AC:
1
AN:
1193944
Hom.:
0
Cov.:
31
AF XY:
0.00000172
AC XY:
1
AN XY:
581518
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000101
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 11, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.178G>A (p.G60R) alteration is located in exon 3 (coding exon 1) of the ZBED3 gene. This alteration results from a G to A substitution at nucleotide position 178, causing the glycine (G) at amino acid position 60 to be replaced by an arginine (R). 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
Uncertain
0.39
BayesDel_addAF
Benign
-0.093
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
19
DANN
Uncertain
0.97
DEOGEN2
Benign
0.096
T;.
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.61
FATHMM_MKL
Benign
0.019
N
LIST_S2
Benign
0.50
T;T
M_CAP
Pathogenic
0.35
D
MetaRNN
Benign
0.20
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.63
N;.
PrimateAI
Pathogenic
0.89
D
PROVEAN
Uncertain
-3.2
D;D
REVEL
Benign
0.11
Sift
Benign
0.30
T;T
Sift4G
Benign
0.38
T;.
Polyphen
0.61
P;.
Vest4
0.30
MutPred
0.63
Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);
MVP
0.030
MPC
1.7
ClinPred
0.36
T
GERP RS
2.9
Varity_R
0.081
gMVP
0.20

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: rs1468430853; hg19: chr5-76373526; API