chr16-72787694-AGCCGCC-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2
The NM_006885.4(ZFHX3):c.10576_10581del(p.Gly3526_Gly3527del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00182 in 1,420,704 control chromosomes in the GnomAD database, including 94 homozygotes. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0027 ( 4 hom., cov: 29)
Exomes 𝑓: 0.0017 ( 90 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 -7 ACMG points.
BP3
?
Nonframeshift variant in repetitive region in NM_006885.4
BP6
?
Variant 16-72787694-AGCCGCC-A is Benign according to our data. Variant chr16-72787694-AGCCGCC-A is described in ClinVar as [Benign]. Clinvar id is 3034404.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-72787694-AGCCGCC-A is described in Lovd as [Likely_benign].
BS2
?
High AC in GnomAd at 405 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFHX3 | NM_006885.4 | c.10576_10581del | p.Gly3526_Gly3527del | inframe_deletion | 10/10 | ENST00000268489.10 | |
ZFHX3-AS1 | NR_171702.1 | n.391-33060_391-33055del | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFHX3 | ENST00000268489.10 | c.10576_10581del | p.Gly3526_Gly3527del | inframe_deletion | 10/10 | 1 | NM_006885.4 | P1 | |
ZFHX3-AS1 | ENST00000687589.1 | n.482+5894_482+5899del | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00273 AC: 405AN: 148442Hom.: 5 Cov.: 29
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GnomAD4 exome AF: 0.00171 AC: 2178AN: 1272160Hom.: 90 AF XY: 0.00185 AC XY: 1154AN XY: 625134
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GnomAD4 genome ? AF: 0.00273 AC: 406AN: 148544Hom.: 4 Cov.: 29 AF XY: 0.00332 AC XY: 240AN XY: 72358
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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 | Sep 10, 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