6-33455834-C-T

Variant summary

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

The NM_152735.4(ZBTB9):​c.734C>T​(p.Pro245Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,459,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.000011 ( 0 hom. )

Consequence

ZBTB9
NM_152735.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.886
Variant links:
Genes affected
ZBTB9 (HGNC:28323): (zinc finger and BTB domain containing 9) Enables identical protein binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06300023).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZBTB9NM_152735.4 linkc.734C>T p.Pro245Leu missense_variant Exon 2 of 2 ENST00000395064.3 NP_689948.1 Q96C00A0A1U9X8U5
ZBTB9XM_047418350.1 linkc.734C>T p.Pro245Leu missense_variant Exon 2 of 2 XP_047274306.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZBTB9ENST00000395064.3 linkc.734C>T p.Pro245Leu missense_variant Exon 2 of 2 1 NM_152735.4 ENSP00000378503.2 Q96C00
ZBTB9ENST00000612407.1 linkc.316C>T p.Pro106Ser missense_variant Exon 2 of 2 3 ENSP00000478118.1 A0A087WTT7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000403
AC:
10
AN:
248284
Hom.:
0
AF XY:
0.0000149
AC XY:
2
AN XY:
134080
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1459010
Hom.:
0
Cov.:
33
AF XY:
0.00000551
AC XY:
4
AN XY:
725642
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000315
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000378
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 17, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.734C>T (p.P245L) alteration is located in exon 2 (coding exon 1) of the ZBTB9 gene. This alteration results from a C to T substitution at nucleotide position 734, causing the proline (P) at amino acid position 245 to be replaced by a leucine (L). 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
0.082
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
16
DANN
Benign
0.57
DEOGEN2
Benign
0.0040
T
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.49
FATHMM_MKL
Benign
0.37
N
LIST_S2
Benign
0.57
T
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.063
T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
1.0
L
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.48
N
REVEL
Benign
0.12
Sift
Benign
0.17
T
Sift4G
Benign
0.46
T
Polyphen
0.041
B
Vest4
0.11
MutPred
0.33
Loss of relative solvent accessibility (P = 0.0676);
MVP
0.28
MPC
0.35
ClinPred
0.051
T
GERP RS
5.4
Varity_R
0.086
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: rs767869213; hg19: chr6-33423611; COSMIC: COSV101221735; COSMIC: COSV101221735; API