3-101676898-C-T

Variant summary

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

The NM_014415.4(ZBTB11):​c.17G>A​(p.Ser6Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,425,108 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

ZBTB11
NM_014415.4 missense

Scores

7
5
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)

Genome browser will be placed here

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=0.40689853).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZBTB11NM_014415.4 linkc.17G>A p.Ser6Asn 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.17G>A p.Ser6Asn missense_variant Exon 1 of 11 1 NM_014415.4 ENSP00000326200.4 O95625

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.02e-7
AC:
1
AN:
1425108
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
704242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.18e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 26, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.17G>A (p.S6N) alteration is located in exon 1 (coding exon 1) of the ZBTB11 gene. This alteration results from a G to A substitution at nucleotide position 17, causing the serine (S) at amino acid position 6 to be replaced by an asparagine (N). 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
Pathogenic
0.73
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Pathogenic
0.14
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.040
T;.
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.41
T;T
MetaSVM
Benign
-0.33
T
MutationAssessor
Benign
1.0
L;.
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-0.76
N;N
REVEL
Benign
0.24
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.39
MutPred
0.26
Gain of glycosylation at S2 (P = 0.0024);Gain of glycosylation at S2 (P = 0.0024);
MVP
0.75
MPC
2.2
ClinPred
0.94
D
GERP RS
5.6
Varity_R
0.41
gMVP
0.79

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: rs1193547904; hg19: chr3-101395742; API