chr6-151366159-C-T

Variant summary

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

The NM_020861.3(ZBTB2):​c.907G>A​(p.Gly303Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000055 ( 0 hom. )

Consequence

ZBTB2
NM_020861.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.45
Variant links:
Genes affected
ZBTB2 (HGNC:20868): (zinc finger and BTB domain containing 2) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and identical protein binding activity. Involved in negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.102944165).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZBTB2NM_020861.3 linkc.907G>A p.Gly303Arg missense_variant Exon 3 of 3 ENST00000325144.5 NP_065912.1 Q8N680

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZBTB2ENST00000325144.5 linkc.907G>A p.Gly303Arg missense_variant Exon 3 of 3 1 NM_020861.3 ENSP00000323183.4 Q8N680

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251414
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000867
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461894
Hom.:
0
Cov.:
34
AF XY:
0.00000413
AC XY:
3
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000624
Hom.:
0
ExAC
AF:
0.0000247
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 10, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.907G>A (p.G303R) alteration is located in exon 3 (coding exon 2) of the ZBTB2 gene. This alteration results from a G to A substitution at nucleotide position 907, causing the glycine (G) at amino acid position 303 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
Benign
0.23
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
20
DANN
Benign
0.89
DEOGEN2
Benign
0.043
T
Eigen
Benign
-0.12
Eigen_PC
Benign
-0.016
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.0087
T
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.55
N
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-0.54
N
REVEL
Benign
0.14
Sift
Benign
0.45
T
Sift4G
Benign
0.53
T
Polyphen
0.43
B
Vest4
0.24
MutPred
0.51
Gain of solvent accessibility (P = 0.019);
MVP
0.15
MPC
0.95
ClinPred
0.069
T
GERP RS
5.8
Varity_R
0.080
gMVP
0.55

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: rs779696416; hg19: chr6-151687294; API