Variant chr1-244053944-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP2

The NM_205768.3(ZBTB18):c.170A>T(p.Tyr57Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZBTB18
NM_205768.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32

Variant links:

Genes affected

ZBTB18 (HGNC:13030): (zinc finger and BTB domain containing 18) This gene encodes a C2H2-type zinc finger protein which acts a transcriptional repressor of genes involved in neuronal development. The encoded protein recognizes a specific sequence motif and recruits components of chromatin to target genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

ZBTB18 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM1

In a domain BTB (size 67) in uniprot entity ZBT18_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_205768.3

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ZBTB18. . Gene score misZ 3.4305 (greater than the threshold 3.09). Trascript score misZ 4.2468 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 22, complex neurodevelopmental disorder.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB18	NM_205768.3 linkuse as main transcript	c.170A>T	p.Tyr57Phe	missense_variant	2/2	ENST00000358704.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB18	ENST00000358704.4 linkuse as main transcript	c.170A>T	p.Tyr57Phe	missense_variant	2/2	1	NM_205768.3	P4	Q99592-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 01, 2022

The c.170A>T (p.Y57F) alteration is located in exon 2 (coding exon 2) of the ZBTB18 gene. This alteration results from a A to T substitution at nucleotide position 170, causing the tyrosine (Y) at amino acid position 57 to be replaced by a phenylalanine (F). 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

Uncertain

0.42

BayesDel_addAF

Uncertain

0.079

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.47

T;.

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.70

D;D

MetaSVM

Benign

-0.36

MutationAssessor

Benign

0.35

N;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.9

.;N

REVEL

Uncertain

0.46

Sift

Benign

0.40

.;T

Sift4G

Benign

0.60

T;T

Polyphen

0.24

B;B

Vest4

0.61

MutPred

0.90

Gain of MoRF binding (P = 0.3873);.;

MVP

0.60

MPC

1.8

ClinPred

0.90

GERP RS

5.0

Varity_R

0.41

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over