19-35716156-C-T

Position:

chr19-35716156-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014383.3(ZBTB32):c.1048C>T(p.His350Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ZBTB32
NM_014383.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.184

Variant links:

Genes affected

ZBTB32 (HGNC:16763): (zinc finger and BTB domain containing 32) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific; identical protein binding activity; and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB32 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03211209).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZBTB32	NM_014383.3 linkuse as main transcript	c.1048C>T	p.His350Tyr	missense_variant	6/7	ENST00000392197.7	NP_055198.1
ZBTB32	NM_001316902.2 linkuse as main transcript	c.217C>T	p.His73Tyr	missense_variant	6/7		NP_001303831.1
ZBTB32	NM_001316903.2 linkuse as main transcript	c.52C>T	p.His18Tyr	missense_variant	5/6		NP_001303832.1
ZBTB32	XM_017026591.2 linkuse as main transcript	c.325C>T	p.His109Tyr	missense_variant	5/6		XP_016882080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZBTB32	ENST00000392197.7 linkuse as main transcript	c.1048C>T	p.His350Tyr	missense_variant	6/7	5	NM_014383.3	ENSP00000376035	P1
ZBTB32	ENST00000262630.7 linkuse as main transcript	c.1048C>T	p.His350Tyr	missense_variant	5/6	1		ENSP00000262630	P1
ZBTB32	ENST00000481182.1 linkuse as main transcript	c.905C>T	p.Ser302Leu	missense_variant, NMD_transcript_variant	3/4	1		ENSP00000433657
ZBTB32	ENST00000426659.6 linkuse as main transcript	c.52C>T	p.His18Tyr	missense_variant	5/6	3		ENSP00000466524

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000521

AC:

AN:

249628

Hom.:

AF XY:

0.0000518

AC XY:

AN XY:

135166

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000708

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:

0.0000185

AC:

AN:

1461574

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000680

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000659

AC:

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

Jun 22, 2023

The c.1048C>T (p.H350Y) alteration is located in exon 5 (coding exon 4) of the ZBTB32 gene. This alteration results from a C to T substitution at nucleotide position 1048, causing the histidine (H) at amino acid position 350 to be replaced by a tyrosine (Y). 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

0.15

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.59

CADD

Benign

8.3

DANN

Benign

0.97

DEOGEN2

Benign

0.21

T;.;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.44

.;T;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.032

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.0

L;.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.10

N;.;N

REVEL

Benign

0.010

Sift

Benign

0.11

T;.;T

Sift4G

Benign

0.32

T;T;T

Polyphen

0.38

B;.;B

Vest4

0.29

MutPred

0.38

Gain of phosphorylation at H350 (P = 0.0241);.;Gain of phosphorylation at H350 (P = 0.0241);

MVP

0.41

MPC

0.11

ClinPred

0.032

GERP RS

1.1

Varity_R

0.053

gMVP

0.17

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