5-77077545-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032367.4(ZBED3):​c.334G>A​(p.Ala112Thr) 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. 13/20 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

ZBED3
NM_032367.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.646
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.056364834).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZBED3NM_032367.4 linkc.334G>A p.Ala112Thr missense_variant Exon 3 of 3 ENST00000255198.3 NP_115743.1 Q96IU2
ZBED3NM_001329564.2 linkc.334G>A p.Ala112Thr 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.334G>A p.Ala112Thr missense_variant Exon 3 of 3 1 NM_032367.4 ENSP00000255198.2 Q96IU2
ENSG00000285000ENST00000646704.1 linkn.1809+15743C>T intron_variant Intron 13 of 15 ENSP00000495089.1 A0A2R8YFF1
ZBED3ENST00000511587.1 linkc.334G>A p.Ala112Thr missense_variant Exon 2 of 2 3 ENSP00000427487.1 D6RIC4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1082132
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
517498
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 17, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.334G>A (p.A112T) 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 334, causing the alanine (A) at amino acid position 112 to be replaced by a threonine (T). 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
0.087
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
0.71
DANN
Benign
0.75
DEOGEN2
Benign
0.0020
T;.
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.013
N
LIST_S2
Benign
0.31
T;T
M_CAP
Uncertain
0.099
D
MetaRNN
Benign
0.056
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.20
N;.
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-0.28
N;N
REVEL
Benign
0.22
Sift
Benign
0.70
T;T
Sift4G
Benign
1.0
T;.
Polyphen
0.0
B;.
Vest4
0.067
MutPred
0.11
Gain of glycosylation at A112 (P = 0.0018);Gain of glycosylation at A112 (P = 0.0018);
MVP
0.030
MPC
1.3
ClinPred
0.036
T
GERP RS
-0.99
Varity_R
0.027
gMVP
0.048

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-76373370; API