14-64522537-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001123329.2(ZBTB1):ā€‹c.1033A>Gā€‹(p.Ile345Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,461,570 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 (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

ZBTB1
NM_001123329.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.40
Variant links:
Genes affected
ZBTB1 (HGNC:20259): (zinc finger and BTB domain containing 1) Enables K63-linked polyubiquitin modification-dependent protein binding activity; protein heterodimerization activity; and protein homodimerization activity. Involved in several processes, including cellular response to UV; nucleobase-containing compound biosynthetic process; and protein homooligomerization. Located in centrosome; nuclear body; and nuclear membrane. [provided by Alliance of Genome Resources, Apr 2022]
HSPA2-AS1 (HGNC:55433): (HSPA2 and ZBTB1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.049661547).
BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZBTB1NM_001123329.2 linkuse as main transcriptc.1033A>G p.Ile345Val missense_variant 2/2 ENST00000683701.1 NP_001116801.1
HSPA2-AS1NR_110550.1 linkuse as main transcriptn.149-3999T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZBTB1ENST00000683701.1 linkuse as main transcriptc.1033A>G p.Ile345Val missense_variant 2/2 NM_001123329.2 ENSP00000506911 P1Q9Y2K1-1
HSPA2-AS1ENST00000554918.1 linkuse as main transcriptn.149-3999T>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250316
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135492
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
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:
0.00000411
AC:
6
AN:
1461570
Hom.:
0
Cov.:
33
AF XY:
0.00000413
AC XY:
3
AN XY:
727096
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1

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 22, 2022The c.1033A>G (p.I345V) alteration is located in exon 2 (coding exon 1) of the ZBTB1 gene. This alteration results from a A to G substitution at nucleotide position 1033, causing the isoleucine (I) at amino acid position 345 to be replaced by a valine (V). 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
0.084
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
14
DANN
Benign
0.87
DEOGEN2
Benign
0.0071
T;.
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.012
FATHMM_MKL
Benign
0.76
D
LIST_S2
Benign
0.78
T;T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.050
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N;N
MutationTaster
Benign
0.54
N;N;N
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
0.28
N;N
REVEL
Benign
0.095
Sift
Benign
0.51
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0
B;B
Vest4
0.076
MutPred
0.45
Loss of stability (P = 0.0689);Loss of stability (P = 0.0689);
MVP
0.068
ClinPred
0.053
T
GERP RS
4.8
Varity_R
0.028
gMVP
0.097

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: rs750991482; hg19: chr14-64989255; API