Genetic Variant ZBTB42:c.*976T>C (chr14-104803442-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001137601.3(ZBTB42):c.*976T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 167,116 control chromosomes in the GnomAD database, including 59,819 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.83 ( 53695 hom., cov: 33)

Exomes 𝑓: 0.90 ( 6124 hom. )

Consequence

ZBTB42
NM_001137601.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.363

Publications

50 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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 rank	MANE	Protein	UniProt
ZBTB42	NM_001137601.3 link	c.*976T>C		3_prime_UTR_variant	Exon 1 of 1	ENST00000342537.8	NP_001131073.1
ZBTB42	NM_001370342.1 link	c.*976T>C		3_prime_UTR_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.*976T>C		3_prime_UTR_variant	Exon 1 of 1	6	NM_001137601.3	ENSP00000409107.2

Frequencies

GnomAD3 genomes

AF:

0.831

AC:

126364

AN:

152024

Hom.:

53656

Cov.:

show subpopulations

Gnomad AFR

AF:

0.778

Gnomad AMI

AF:

0.888

Gnomad AMR

AF:

0.780

Gnomad ASJ

AF:

0.887

Gnomad EAS

AF:

0.329

Gnomad SAS

AF:

0.654

Gnomad FIN

AF:

0.909

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.910

Gnomad OTH

AF:

0.841

GnomAD4 exome

AF:

0.904

AC:

13534

AN:

14972

Hom.:

6124

Cov.:

AF XY:

0.902

AC XY:

6476

AN XY:

7180

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AF:

0.700

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.357

AC:

AN:

South Asian (SAS)

AF:

0.813

AC:

AN:

European-Finnish (FIN)

AF:

0.905

AC:

13008

AN:

14378

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.914

AC:

402

AN:

440

Other (OTH)

AF:

0.872

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

105

158

210

263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.831

AC:

126470

AN:

152144

Hom.:

53695

Cov.:

AF XY:

0.825

AC XY:

61361

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.778

AC:

32281

AN:

41494

American (AMR)

AF:

0.780

AC:

11925

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.887

AC:

3081

AN:

3472

East Asian (EAS)

AF:

0.330

AC:

1700

AN:

5148

South Asian (SAS)

AF:

0.656

AC:

3168

AN:

4828

European-Finnish (FIN)

AF:

0.909

AC:

9645

AN:

10616

Middle Eastern (MID)

AF:

0.806

AC:

237

AN:

294

European-Non Finnish (NFE)

AF:

0.910

AC:

61855

AN:

67974

Other (OTH)

AF:

0.838

AC:

1768

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1026

2051

3077

4102

5128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

874

1748

2622

3496

4370

<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:

0.873

Hom.:

149295

Bravo

AF:

0.820

Asia WGS

AF:

0.508

AC:

1772

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

6.7

(source)

DANN

Benign

0.79

PhyloP100

-0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Computational scores

Splicing

Publications

Other links and lift over