Variant 14-104801808-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001137601.3(ZBTB42):c.611C>T(p.Pro204Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000942 in 1,549,922 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00052 ( 1 hom., cov: 34)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

ZBTB42
NM_001137601.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.21

Variant links:

Genes affected

ZBTB42 (HGNC:32550): (zinc finger and BTB domain containing 42) The protein encoded by this gene is a member of the C2H2 zinc finger protein family. This protein is predicted to have a pox virus and zinc finger (POZ) domain at the N-terminus and four zinc finger domains at the C-terminus. In human and mouse, the protein localizes to the nuclei of skeletal muscle cells. Knockdown of this gene in zebrafish results in abnormal skeletal muscle development and myofibrillar disorganization. A novel homozygous variant of the human gene has been associated with lethal congenital contracture syndrome, an autosomal recessive disorder that results in muscle wasting. [provided by RefSeq, Mar 2015]

ZBTB42 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=0.011176139).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB42	NM_001137601.3 linkuse as main transcript	c.611C>T	p.Pro204Leu	missense_variant	1/1	ENST00000342537.8
ZBTB42	NM_001370342.1 linkuse as main transcript	c.611C>T	p.Pro204Leu	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB42	ENST00000342537.8 linkuse as main transcript	c.611C>T	p.Pro204Leu	missense_variant	1/1		NM_001137601.3	P1
ZBTB42	ENST00000555360.1 linkuse as main transcript	c.611C>T	p.Pro204Leu	missense_variant	2/2	1		P1

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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:

0.000105

AC:

AN:

152496

Hom.:

AF XY:

0.0000861

AC XY:

AN XY:

81272

show subpopulations

Gnomad AFR exome

AF:

0.00193

Gnomad AMR exome

AF:

0.0000406

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:

0.0000479

AC:

AN:

1397676

Hom.:

Cov.:

AF XY:

0.0000508

AC XY:

AN XY:

689308

show subpopulations

Gnomad4 AFR exome

AF:

0.00142

Gnomad4 AMR exome

AF:

0.0000841

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:

0.0000148

Gnomad4 OTH exome

AF:

0.0000518

GnomAD4 genome

AF:

0.000519

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00191

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000263

Hom.:

Bravo

AF:

0.000518

ExAC

AF:

0.000211

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

Dec 07, 2021

The c.611C>T (p.P204L) alteration is located in exon 2 (coding exon 1) of the ZBTB42 gene. This alteration results from a C to T substitution at nucleotide position 611, causing the proline (P) at amino acid position 204 to be replaced by a leucine (L). 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

0.21

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.046

T;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.93

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.3

D;D

REVEL

Benign

0.13

Sift

Uncertain

0.014

D;D

Sift4G

Benign

0.18

T;T

Polyphen

0.85

P;P

Vest4

0.10

MVP

0.15

ClinPred

0.11

GERP RS

3.5

Varity_R

0.16

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