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14-104801242-A-G

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

2

Clinical Significance

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

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.42 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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
ZBTB42NM_001137601.3 linkuse as main transcriptc.45A>G p.Arg15= synonymous_variant 1/1 ENST00000342537.8
ZBTB42NM_001370342.1 linkuse as main transcriptc.45A>G p.Arg15= synonymous_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZBTB42ENST00000342537.8 linkuse as main transcriptc.45A>G p.Arg15= synonymous_variant 1/1 NM_001137601.3 P1
ZBTB42ENST00000555360.1 linkuse as main transcriptc.45A>G p.Arg15= synonymous_variant 2/21 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.836
AC:
127114
AN:
152132
Hom.:
54214
Cov.:
36
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.:
68
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.836
AC:
127223
AN:
152250
Hom.:
54257
Cov.:
36
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:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 13, 2018- -
Lethal congenital contracture syndrome 6 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabDec 05, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
Cadd
Benign
14
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.

Other links and lift over

dbSNP: rs12878684; hg19: chr14-105267579; COSMIC: COSV61136985; API