3-101676902-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014415.4(ZBTB11):​c.13G>A​(p.Glu5Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ZBTB11
NM_014415.4 missense

Scores

5
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.23
Variant links:
Genes affected
ZBTB11 (HGNC:16740): (zinc finger and BTB domain containing 11) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Located in nucleoplasm. Implicated in autosomal recessive non-syndromic intellectual disability. [provided by Alliance of Genome Resources, Apr 2022]
ZBTB11-AS1 (HGNC:48573): (ZBTB11 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33392358).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZBTB11NM_014415.4 linkc.13G>A p.Glu5Lys missense_variant Exon 1 of 11 ENST00000312938.5 NP_055230.2 O95625Q59H97

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZBTB11ENST00000312938.5 linkc.13G>A p.Glu5Lys missense_variant Exon 1 of 11 1 NM_014415.4 ENSP00000326200.4 O95625

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Feb 15, 2022
GeneDx
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.76
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.010
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.036
T;.
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Uncertain
0.17
D
MetaRNN
Benign
0.33
T;T
MetaSVM
Benign
-0.33
T
MutationAssessor
Benign
0.63
N;.
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-0.86
N;N
REVEL
Uncertain
0.29
Sift
Pathogenic
0.0
D;D
Sift4G
Benign
0.091
T;T
Polyphen
0.91
P;P
Vest4
0.38
MutPred
0.34
Gain of MoRF binding (P = 0);Gain of MoRF binding (P = 0);
MVP
0.82
MPC
1.9
ClinPred
0.82
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.45
gMVP
0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-101395746; API