chr16-72787694-AGCCGCCGCC-A
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3BP6_ModerateBS1BS2
The NM_006885.4(ZFHX3):c.10573_10581del(p.Gly3525_Gly3527del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0329 in 1,420,694 control chromosomes in the GnomAD database, including 3,693 homozygotes. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.021 ( 44 hom., cov: 29)
Exomes 𝑓: 0.034 ( 3649 hom. )
Consequence
ZFHX3
NM_006885.4 inframe_deletion
NM_006885.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.41
Genes affected
ZFHX3 (HGNC:777): (zinc finger homeobox 3) This gene encodes a transcription factor with multiple homeodomains and zinc finger motifs, and regulates myogenic and neuronal differentiation. The encoded protein suppresses expression of the alpha-fetoprotein gene by binding to an AT-rich enhancer motif. The protein has also been shown to negatively regulate c-Myb, and transactivate the cell cycle inhibitor cyclin-dependent kinase inhibitor 1A (also known as p21CIP1). This gene is reported to function as a tumor suppressor in several cancers, and sequence variants of this gene are also associated with atrial fibrillation. Multiple transcript variants expressed from alternate promoters and encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP3
?
Nonframeshift variant in repetitive region in NM_006885.4
BP6
?
Variant 16-72787694-AGCCGCCGCC-A is Benign according to our data. Variant chr16-72787694-AGCCGCCGCC-A is described in ClinVar as [Benign]. Clinvar id is 3058928.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-72787694-AGCCGCCGCC-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0211 (3132/148526) while in subpopulation NFE AF= 0.0276 (1848/66906). AF 95% confidence interval is 0.0266. There are 44 homozygotes in gnomad4. There are 1506 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
BS2
?
High AC in GnomAd at 3132 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFHX3 | NM_006885.4 | c.10573_10581del | p.Gly3525_Gly3527del | inframe_deletion | 10/10 | ENST00000268489.10 | |
ZFHX3-AS1 | NR_171702.1 | n.391-33063_391-33055del | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFHX3 | ENST00000268489.10 | c.10573_10581del | p.Gly3525_Gly3527del | inframe_deletion | 10/10 | 1 | NM_006885.4 | P1 | |
ZFHX3-AS1 | ENST00000687589.1 | n.482+5891_482+5899del | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0211 AC: 3132AN: 148424Hom.: 44 Cov.: 29
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GnomAD4 exome AF: 0.0343 AC: 43600AN: 1272168Hom.: 3649 AF XY: 0.0347 AC XY: 21678AN XY: 625152
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
ZFHX3-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 05, 2019 | 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
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at