19-35715026-C-T

Variant summary

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

The NM_014383.3(ZBTB32):​c.400C>T​(p.Pro134Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P134T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZBTB32
NM_014383.3 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.292
Variant links:
Genes affected
ZBTB32 (HGNC:16763): (zinc finger and BTB domain containing 32) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific; identical protein binding activity; and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.053474605).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZBTB32NM_014383.3 linkc.400C>T p.Pro134Ser missense_variant Exon 3 of 7 ENST00000392197.7 NP_055198.1 Q9Y2Y4
ZBTB32NM_001316902.2 linkc.6-437C>T intron_variant Intron 2 of 6 NP_001303831.1 Q9Y2Y4
ZBTB32NM_001316903.2 linkc.-86-437C>T intron_variant Intron 2 of 5 NP_001303832.1 Q9Y2Y4
ZBTB32XM_017026591.2 linkc.6-437C>T intron_variant Intron 2 of 5 XP_016882080.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZBTB32ENST00000392197.7 linkc.400C>T p.Pro134Ser missense_variant Exon 3 of 7 5 NM_014383.3 ENSP00000376035.1 Q9Y2Y4
ZBTB32ENST00000262630.7 linkc.400C>T p.Pro134Ser missense_variant Exon 2 of 6 1 ENSP00000262630.3 Q9Y2Y4
ZBTB32ENST00000481182.1 linkn.400C>T non_coding_transcript_exon_variant Exon 2 of 4 1 ENSP00000433657.1 A0A0C4DGF1
ZBTB32ENST00000426659.6 linkc.-86-437C>T intron_variant Intron 2 of 5 3 ENSP00000466524.1 K7EMJ1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000808
AC:
2
AN:
247534
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134172
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000655
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460210
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726508
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.0000247
AC:
3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
9.9
DANN
Uncertain
0.99
DEOGEN2
Benign
0.17
T;T
Eigen
Benign
-0.79
Eigen_PC
Benign
-0.76
FATHMM_MKL
Benign
0.055
N
LIST_S2
Benign
0.64
.;T
M_CAP
Benign
0.0066
T
MetaRNN
Benign
0.053
T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.8
L;L
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.60
N;N
REVEL
Benign
0.019
Sift
Uncertain
0.026
D;D
Sift4G
Benign
0.40
T;T
Polyphen
0.062
B;B
Vest4
0.11
MutPred
0.19
Gain of phosphorylation at P134 (P = 0.0024);Gain of phosphorylation at P134 (P = 0.0024);
MVP
0.28
MPC
0.31
ClinPred
0.18
T
GERP RS
3.0
Varity_R
0.033
gMVP
0.17

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: rs767597336; hg19: chr19-36205928; API