rs34284721

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001137601.3(ZBTB42):c.400G>A(p.Ala134Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,549,842 control chromosomes in the GnomAD database, including 9,323 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 766 hom., cov: 34)

Exomes 𝑓: 0.11 ( 8557 hom. )

Consequence

ZBTB42
NM_001137601.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.356

Publications

14 publications found

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 Gene-Disease associations (from GenCC):

lethal congenital contracture syndrome 6
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ZBTB42 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015160143).

BP6

Variant 14-104801597-G-A is Benign according to our data. Variant chr14-104801597-G-A is described in ClinVar as [Benign]. Clinvar id is 1266544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB42	NM_001137601.3 link	c.400G>A	p.Ala134Thr	missense_variant	Exon 1 of 1	ENST00000342537.8	NP_001131073.1	B2RXF5
ZBTB42	NM_001370342.1 link	c.400G>A	p.Ala134Thr	missense_variant	Exon 2 of 2		NP_001357271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB42	ENST00000342537.8 link	c.400G>A	p.Ala134Thr	missense_variant	Exon 1 of 1	6	NM_001137601.3	ENSP00000409107.2		B2RXF5
ZBTB42	ENST00000555360.1 link	c.400G>A	p.Ala134Thr	missense_variant	Exon 2 of 2	1		ENSP00000450673.1		B2RXF5

Frequencies

GnomAD3 genomes

AF:

0.0846

AC:

12863

AN:

152110

Hom.:

766

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0188

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.0784

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0540

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.0880

GnomAD2 exomes

AF:

0.0925

AC:

13771

AN:

148924

AF XY:

0.0940

show subpopulations

Gnomad AFR exome

AF:

0.0148

Gnomad AMR exome

AF:

0.0615

Gnomad ASJ exome

AF:

0.161

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.144

Gnomad NFE exome

AF:

0.119

Gnomad OTH exome

AF:

0.112

GnomAD4 exome

AF:

0.106

AC:

147994

AN:

1397614

Hom.:

8557

Cov.:

AF XY:

0.106

AC XY:

73118

AN XY:

689254

show subpopulations

African (AFR)

AF:

0.0154

AC:

485

AN:

31596

American (AMR)

AF:

0.0655

AC:

2335

AN:

35672

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

4103

AN:

25164

East Asian (EAS)

AF:

0.000196

AC:

AN:

35730

South Asian (SAS)

AF:

0.0680

AC:

5390

AN:

79220

European-Finnish (FIN)

AF:

0.143

AC:

6842

AN:

47886

Middle Eastern (MID)

AF:

0.0862

AC:

491

AN:

5696

European-Non Finnish (NFE)

AF:

0.114

AC:

122674

AN:

1078682

Other (OTH)

AF:

0.0978

AC:

5667

AN:

57968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

8793

17586

26378

35171

43964

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0845

AC:

12863

AN:

152228

Hom.:

766

Cov.:

AF XY:

0.0848

AC XY:

6314

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0188

AC:

779

AN:

41546

American (AMR)

AF:

0.0783

AC:

1198

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

628

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5174

South Asian (SAS)

AF:

0.0545

AC:

263

AN:

4828

European-Finnish (FIN)

AF:

0.142

AC:

1511

AN:

10606

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.120

AC:

8133

AN:

67980

Other (OTH)

AF:

0.0875

AC:

185

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

600

1200

1801

2401

3001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.109

Hom.:

1371

Bravo

AF:

0.0776

TwinsUK

AF:

0.123

AC:

455

ALSPAC

AF:

0.111

AC:

427

ESP6500AA

AF:

0.0210

AC:

ESP6500EA

AF:

0.118

AC:

376

ExAC

AF:

0.0716

AC:

1903

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ZBTB42-related disorder

Benign:1

Jun 28, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.9

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.0027

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.43

.;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.81

L;L

PhyloP100

0.36

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.51

N;N

REVEL

Benign

0.023

Sift

Benign

0.61

T;T

Sift4G

Benign

0.59

T;T

Polyphen

0.0030

B;B

Vest4

0.021

ClinPred

0.0014

GERP RS

-2.4

PromoterAI

-0.021

Neutral

(source)

Varity_R

0.026

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs34284721

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over