17-7462605-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001128833.2(ZBTB4):​c.2377G>A​(p.Gly793Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000096 in 1,457,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

ZBTB4
NM_001128833.2 missense

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90
Variant links:
Genes affected
ZBTB4 (HGNC:23847): (zinc finger and BTB domain containing 4) Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; methyl-CpNpG binding activity; and sequence-specific DNA binding activity. Involved in cellular response to DNA damage stimulus and negative regulation of transcription by RNA polymerase II. Located in cytosol and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.24952006).
BS2
High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZBTB4NM_001128833.2 linkc.2377G>A p.Gly793Arg missense_variant 4/4 ENST00000380599.9 NP_001122305.1 Q9P1Z0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZBTB4ENST00000380599.9 linkc.2377G>A p.Gly793Arg missense_variant 4/41 NM_001128833.2 ENSP00000369973.4 Q9P1Z0
ZBTB4ENST00000311403.4 linkc.2377G>A p.Gly793Arg missense_variant 4/41 ENSP00000307858.4 Q9P1Z0

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000960
AC:
14
AN:
1457776
Hom.:
0
Cov.:
31
AF XY:
0.00000690
AC XY:
5
AN XY:
724982
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.0000117
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 19, 2024The c.2377G>A (p.G793R) alteration is located in exon 4 (coding exon 2) of the ZBTB4 gene. This alteration results from a G to A substitution at nucleotide position 2377, causing the glycine (G) at amino acid position 793 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
0.27
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.023
T;T
Eigen
Benign
0.027
Eigen_PC
Benign
0.092
FATHMM_MKL
Benign
0.63
D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.25
T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
0.69
N;N
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.085
Sift
Uncertain
0.0060
D;D
Sift4G
Benign
0.10
T;T
Polyphen
0.89
P;P
Vest4
0.53
MutPred
0.40
Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);
MVP
0.082
MPC
0.54
ClinPred
0.57
D
GERP RS
4.1
Varity_R
0.096
gMVP
0.44

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: rs34327669; hg19: chr17-7365924; API