Genetic Variant ZBTB42:p.Leu190Leu (chr14-104801767-G-A) – ACMG Classification: Benign (-20 pts)

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.570G>A(p.Leu190Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.274 in 1,548,706 control chromosomes in the GnomAD database, including 59,318 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6127 hom., cov: 34)

Exomes 𝑓: 0.27 ( 53191 hom. )

Consequence

ZBTB42
NM_001137601.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.02

Publications

19 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 (BayesDel_noAF=-0.59).

BP6

Variant 14-104801767-G-A is Benign according to our data. Variant chr14-104801767-G-A is described in ClinVar as Benign. ClinVar VariationId is 1260467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB42	NM_001137601.3 link	c.570G>A	p.Leu190Leu	synonymous_variant	Exon 1 of 1	ENST00000342537.8	NP_001131073.1	B2RXF5
ZBTB42	NM_001370342.1 link	c.570G>A	p.Leu190Leu	synonymous_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.570G>A	p.Leu190Leu	synonymous_variant	Exon 1 of 1	6	NM_001137601.3	ENSP00000409107.2		B2RXF5
ZBTB42	ENST00000555360.1 link	c.570G>A	p.Leu190Leu	synonymous_variant	Exon 2 of 2	1		ENSP00000450673.1		B2RXF5

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

42125

AN:

152046

Hom.:

6116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.252

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.265

GnomAD2 exomes

AF:

0.242

AC:

36710

AN:

151526

AF XY:

0.242

show subpopulations

Gnomad AFR exome

AF:

0.320

Gnomad AMR exome

AF:

0.197

Gnomad ASJ exome

AF:

0.229

Gnomad EAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.293

Gnomad NFE exome

AF:

0.282

Gnomad OTH exome

AF:

0.257

GnomAD4 exome

AF:

0.274

AC:

382272

AN:

1396542

Hom.:

53191

Cov.:

AF XY:

0.271

AC XY:

186906

AN XY:

688572

show subpopulations

African (AFR)

AF:

0.316

AC:

9964

AN:

31568

American (AMR)

AF:

0.208

AC:

7416

AN:

35588

Ashkenazi Jewish (ASJ)

AF:

0.235

AC:

5895

AN:

25132

East Asian (EAS)

AF:

0.138

AC:

4944

AN:

35714

South Asian (SAS)

AF:

0.194

AC:

15354

AN:

79068

European-Finnish (FIN)

AF:

0.292

AC:

13991

AN:

47848

Middle Eastern (MID)

AF:

0.186

AC:

1056

AN:

5688

European-Non Finnish (NFE)

AF:

0.286

AC:

308660

AN:

1078046

Other (OTH)

AF:

0.259

AC:

14992

AN:

57890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

18344

36688

55033

73377

91721

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10332

20664

30996

41328

51660

<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:

0.277

AC:

42172

AN:

152164

Hom.:

6127

Cov.:

AF XY:

0.275

AC XY:

20428

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.311

AC:

12917

AN:

41504

American (AMR)

AF:

0.236

AC:

3603

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

874

AN:

3472

East Asian (EAS)

AF:

0.107

AC:

552

AN:

5180

South Asian (SAS)

AF:

0.176

AC:

850

AN:

4822

European-Finnish (FIN)

AF:

0.292

AC:

3091

AN:

10594

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.286

AC:

19424

AN:

67984

Other (OTH)

AF:

0.266

AC:

562

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1559

3118

4677

6236

7795

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<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:

0.255

Hom.:

2938

Bravo

AF:

0.276

Asia WGS

AF:

0.135

AC:

466

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

Nov 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

9.5

(source)

DANN

Benign

0.81

PhyloP100

4.0

Mutation Taster

=96/4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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