19-58516599-C-T

Variant summary

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

The NM_001316979.2(ZBTB45):​c.1075G>A​(p.Ala359Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000503 in 1,431,652 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000035 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

ZBTB45
NM_001316979.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.80
Variant links:
Genes affected
ZBTB45 (HGNC:23715): (zinc finger and BTB domain containing 45) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in 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 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=0.033112198).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZBTB45NM_001316979.2 linkc.1075G>A p.Ala359Thr missense_variant Exon 2 of 3 ENST00000594051.6 NP_001303908.1 Q96K62A0A024R4T8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZBTB45ENST00000594051.6 linkc.1075G>A p.Ala359Thr missense_variant Exon 2 of 3 2 NM_001316979.2 ENSP00000469089.1 Q96K62
ZBTB45ENST00000354590.7 linkc.1075G>A p.Ala359Thr missense_variant Exon 2 of 3 1 ENSP00000346603.2 Q96K62
ZBTB45ENST00000600990.1 linkc.1075G>A p.Ala359Thr missense_variant Exon 2 of 3 5 ENSP00000473072.1 Q96K62

Frequencies

GnomAD3 genomes
AF:
0.0000347
AC:
5
AN:
144012
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000257
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000138
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000303
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000535
AC:
10
AN:
186922
Hom.:
0
AF XY:
0.0000594
AC XY:
6
AN XY:
101062
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000148
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000622
Gnomad SAS exome
AF:
0.000139
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000241
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000520
AC:
67
AN:
1287640
Hom.:
0
Cov.:
33
AF XY:
0.0000552
AC XY:
35
AN XY:
634398
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000860
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000662
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000516
Gnomad4 OTH exome
AF:
0.0000199
GnomAD4 genome
AF:
0.0000347
AC:
5
AN:
144012
Hom.:
0
Cov.:
32
AF XY:
0.0000143
AC XY:
1
AN XY:
70008
show subpopulations
Gnomad4 AFR
AF:
0.0000257
Gnomad4 AMR
AF:
0.000138
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000303
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
ExAC
AF:
0.0000167
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 01, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1075G>A (p.A359T) alteration is located in exon 2 (coding exon 1) of the ZBTB45 gene. This alteration results from a G to A substitution at nucleotide position 1075, causing the alanine (A) at amino acid position 359 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
0.11
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
0.063
DANN
Benign
0.89
DEOGEN2
Benign
0.016
T;T;T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.042
N
LIST_S2
Benign
0.58
.;.;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.033
T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.14
N;N;N
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
0.020
N;.;.
REVEL
Benign
0.0030
Sift
Benign
0.41
T;.;.
Sift4G
Benign
0.69
T;T;T
Polyphen
0.0
B;B;B
Vest4
0.090
MutPred
0.25
Gain of glycosylation at A359 (P = 0);Gain of glycosylation at A359 (P = 0);Gain of glycosylation at A359 (P = 0);
MVP
0.13
MPC
0.35
ClinPred
0.13
T
GERP RS
-6.3
Varity_R
0.034
gMVP
0.14

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: rs539670110; hg19: chr19-59027966; API