Variant chr14-104801242-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001137601.3(ZBTB42):c.45A>G(p.Arg15=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 1,481,248 control chromosomes in the GnomAD database, including 573,972 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 54257 hom., cov: 36)

Exomes 𝑓: 0.88 ( 519715 hom. )

Consequence

ZBTB42
NM_001137601.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.42

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 14-104801242-A-G is Benign according to our data. Variant chr14-104801242-A-G is described in ClinVar as [Benign]. Clinvar id is 1246843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.42 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB42	NM_001137601.3 linkuse as main transcript	c.45A>G	p.Arg15=	synonymous_variant	1/1	ENST00000342537.8
ZBTB42	NM_001370342.1 linkuse as main transcript	c.45A>G	p.Arg15=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB42	ENST00000342537.8 linkuse as main transcript	c.45A>G	p.Arg15=	synonymous_variant	1/1		NM_001137601.3	P1
ZBTB42	ENST00000555360.1 linkuse as main transcript	c.45A>G	p.Arg15=	synonymous_variant	2/2	1		P1

Frequencies

GnomAD3 genomes

AF:

0.836

AC:

127114

AN:

152132

Hom.:

54214

Cov.:

show subpopulations

Gnomad AFR

AF:

0.793

Gnomad AMI

AF:

0.887

Gnomad AMR

AF:

0.780

Gnomad ASJ

AF:

0.887

Gnomad EAS

AF:

0.327

Gnomad SAS

AF:

0.659

Gnomad FIN

AF:

0.909

Gnomad MID

AF:

0.813

Gnomad NFE

AF:

0.910

Gnomad OTH

AF:

0.841

GnomAD3 exomes

AF:

0.766

AC:

68637

AN:

89556

Hom.:

27836

AF XY:

0.771

AC XY:

37214

AN XY:

48248

show subpopulations

Gnomad AFR exome

AF:

0.792

Gnomad AMR exome

AF:

0.707

Gnomad ASJ exome

AF:

0.870

Gnomad EAS exome

AF:

0.304

Gnomad SAS exome

AF:

0.678

Gnomad FIN exome

AF:

0.895

Gnomad NFE exome

AF:

0.907

Gnomad OTH exome

AF:

0.829

GnomAD4 exome

AF:

0.878

AC:

1167048

AN:

1328998

Hom.:

519715

Cov.:

AF XY:

0.874

AC XY:

568108

AN XY:

650036

show subpopulations

Gnomad4 AFR exome

AF:

0.785

Gnomad4 AMR exome

AF:

0.724

Gnomad4 ASJ exome

AF:

0.876

Gnomad4 EAS exome

AF:

0.397

Gnomad4 SAS exome

AF:

0.697

Gnomad4 FIN exome

AF:

0.900

Gnomad4 NFE exome

AF:

0.914

Gnomad4 OTH exome

AF:

0.844

GnomAD4 genome

AF:

0.836

AC:

127223

AN:

152250

Hom.:

54257

Cov.:

AF XY:

0.829

AC XY:

61693

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.793

Gnomad4 AMR

AF:

0.780

Gnomad4 ASJ

AF:

0.887

Gnomad4 EAS

AF:

0.328

Gnomad4 SAS

AF:

0.660

Gnomad4 FIN

AF:

0.909

Gnomad4 NFE

AF:

0.910

Gnomad4 OTH

AF:

0.838

Alfa

AF:

0.873

Hom.:

10669

Bravo

AF:

0.825

Asia WGS

AF:

0.512

AC:

1782

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 13, 2018	- -

Lethal congenital contracture syndrome 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.80

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