rs4983387

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.694G>A(p.Glu232Lys) variant causes a missense change. The variant allele was found at a frequency of 0.845 in 1,548,540 control chromosomes in the GnomAD database, including 565,078 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 47407 hom., cov: 34)

Exomes 𝑓: 0.85 ( 517671 hom. )

Consequence

ZBTB42
NM_001137601.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 6.95

Publications

44 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=9.088913E-7).

BP6

Variant 14-104801891-G-A is Benign according to our data. Variant chr14-104801891-G-A is described in ClinVar as Benign. ClinVar VariationId is 803053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB42	NM_001137601.3 link	c.694G>A	p.Glu232Lys	missense_variant	Exon 1 of 1	ENST00000342537.8	NP_001131073.1	B2RXF5
ZBTB42	NM_001370342.1 link	c.694G>A	p.Glu232Lys	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.694G>A	p.Glu232Lys	missense_variant	Exon 1 of 1	6	NM_001137601.3	ENSP00000409107.2		B2RXF5
ZBTB42	ENST00000555360.1 link	c.694G>A	p.Glu232Lys	missense_variant	Exon 2 of 2	1		ENSP00000450673.1		B2RXF5

Frequencies

GnomAD3 genomes

AF:

0.774

AC:

117702

AN:

152104

Hom.:

47375

Cov.:

show subpopulations

Gnomad AFR

AF:

0.625

Gnomad AMI

AF:

0.889

Gnomad AMR

AF:

0.744

Gnomad ASJ

AF:

0.874

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.581

Gnomad FIN

AF:

0.898

Gnomad MID

AF:

0.747

Gnomad NFE

AF:

0.893

Gnomad OTH

AF:

0.794

GnomAD2 exomes

AF:

0.756

AC:

114196

AN:

151048

AF XY:

0.759

show subpopulations

Gnomad AFR exome

AF:

0.620

Gnomad AMR exome

AF:

0.669

Gnomad ASJ exome

AF:

0.866

Gnomad EAS exome

AF:

0.297

Gnomad FIN exome

AF:

0.893

Gnomad NFE exome

AF:

0.894

Gnomad OTH exome

AF:

0.811

GnomAD4 exome

AF:

0.853

AC:

1190811

AN:

1396318

Hom.:

517671

Cov.:

AF XY:

0.848

AC XY:

584037

AN XY:

688778

show subpopulations

African (AFR)

AF:

0.614

AC:

19385

AN:

31588

American (AMR)

AF:

0.682

AC:

24325

AN:

35680

Ashkenazi Jewish (ASJ)

AF:

0.863

AC:

21739

AN:

25180

East Asian (EAS)

AF:

0.378

AC:

13524

AN:

35734

South Asian (SAS)

AF:

0.633

AC:

50164

AN:

79210

European-Finnish (FIN)

AF:

0.892

AC:

41402

AN:

46436

Middle Eastern (MID)

AF:

0.766

AC:

4363

AN:

5698

European-Non Finnish (NFE)

AF:

0.898

AC:

969020

AN:

1078826

Other (OTH)

AF:

0.809

AC:

46889

AN:

57966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

10233

20466

30699

40932

51165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20888

41776

62664

83552

104440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.774

AC:

117794

AN:

152222

Hom.:

47407

Cov.:

AF XY:

0.768

AC XY:

57165

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.625

AC:

25955

AN:

41514

American (AMR)

AF:

0.744

AC:

11392

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.874

AC:

3034

AN:

3470

East Asian (EAS)

AF:

0.312

AC:

1614

AN:

5168

South Asian (SAS)

AF:

0.583

AC:

2806

AN:

4816

European-Finnish (FIN)

AF:

0.898

AC:

9532

AN:

10620

Middle Eastern (MID)

AF:

0.755

AC:

222

AN:

294

European-Non Finnish (NFE)

AF:

0.893

AC:

60756

AN:

68006

Other (OTH)

AF:

0.791

AC:

1674

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1232

2464

3697

4929

6161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

844

1688

2532

3376

4220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.852

Hom.:

90566

Bravo

AF:

0.757

TwinsUK

AF:

0.903

AC:

3347

ALSPAC

AF:

0.903

AC:

3481

ESP6500AA

AF:

0.624

AC:

864

ESP6500EA

AF:

0.901

AC:

2860

ExAC

AF:

0.722

AC:

15747

Asia WGS

AF:

0.444

AC:

1545

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Lethal congenital contracture syndrome 6

Benign:2

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

T;T

Eigen

Benign

-0.078

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.82

.;T

MetaRNN

Benign

9.1e-7

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;L

PhyloP100

7.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.16

Sift

Uncertain

0.0080

D;D

Sift4G

Benign

0.52

T;T

Polyphen

0.98

D;D

Vest4

0.057

ClinPred

0.063

GERP RS

3.7

Varity_R

0.083

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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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