14-64522537-A-G
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001123329.2(ZBTB1):āc.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
NM_001123329.2 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 5.40
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]
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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 |
---|---|---|---|---|---|---|---|---|
ZBTB1 | NM_001123329.2 | c.1033A>G | p.Ile345Val | missense_variant | 2/2 | ENST00000683701.1 | NP_001116801.1 | |
HSPA2-AS1 | NR_110550.1 | n.149-3999T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZBTB1 | ENST00000683701.1 | c.1033A>G | p.Ile345Val | missense_variant | 2/2 | NM_001123329.2 | ENSP00000506911 | P1 | ||
HSPA2-AS1 | ENST00000554918.1 | n.149-3999T>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250316Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135492
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461570Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727096
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GnomAD4 genome Cov.: 33
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33
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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 submitter | clinical testing | Ambry Genetics | Apr 22, 2022 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Loss of stability (P = 0.0689);Loss of stability (P = 0.0689);
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at