Variant chr11-114063829-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_006006.6(ZBTB16):c.529C>T(p.Pro177Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,808 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: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZBTB16
NM_006006.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.462

Variant links:

Genes affected

ZBTB16 (HGNC:12930): (zinc finger and BTB domain containing 16) This gene is a member of the Krueppel C2H2-type zinc-finger protein family and encodes a zinc finger transcription factor that contains nine Kruppel-type zinc finger domains at the carboxyl terminus. This protein is located in the nucleus, is involved in cell cycle progression, and interacts with a histone deacetylase. Specific instances of aberrant gene rearrangement at this locus have been associated with acute promyelocytic leukemia (APL). Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

ZBTB16 links:

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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;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ZBTB16. . Gene score misZ 2.4714 (greater than the threshold 3.09). Trascript score misZ 3.8406 (greater than threshold 3.09). GenCC has associacion of gene with skeletal defects, genital hypoplasia, and intellectual disability.

BP4

Computational evidence support a benign effect (MetaRNN=0.07106319).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB16	NM_006006.6 linkuse as main transcript	c.529C>T	p.Pro177Ser	missense_variant	2/7	ENST00000335953.9	NP_005997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB16	ENST00000335953.9 linkuse as main transcript	c.529C>T	p.Pro177Ser	missense_variant	2/7	1	NM_006006.6	ENSP00000338157	P1	Q05516-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251378

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000137

AC:

AN:

1461808

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Jan 02, 2024

The c.529C>T (p.P177S) alteration is located in exon 2 (coding exon 1) of the ZBTB16 gene. This alteration results from a C to T substitution at nucleotide position 529, causing the proline (P) at amino acid position 177 to be replaced by a serine (S). 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

0.078

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

T;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.74

.;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.071

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.90

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.63

N;N

REVEL

Benign

0.027

Sift

Uncertain

0.017

D;D

Sift4G

Benign

0.085

T;T

Polyphen

0.0050

B;B

Vest4

0.11

MutPred

0.47

Gain of glycosylation at P177 (P = 0.0232);Gain of glycosylation at P177 (P = 0.0232);

MVP

0.22

MPC

0.59

ClinPred

0.11

GERP RS

2.7

Varity_R

0.075

gMVP

0.39

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over