16-72788110-TGCTGCTGCTGCTGCTGTAGTTGCC-TGCTGCTGCTGCTGCTGTAGTTGCCGCTGCTGCTGCTGCTGTAGTTGCC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006885.4(ZFHX3):​c.10142_10165dupGGCAACTACAGCAGCAGCAGCAGC​(p.Arg3381_Gln3388dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,599,246 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ZFHX3
NM_006885.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.680
Variant links:
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]
ZFHX3-AS1 (HGNC:56033): (ZFHX3 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZFHX3NM_006885.4 linkc.10142_10165dupGGCAACTACAGCAGCAGCAGCAGC p.Arg3381_Gln3388dup conservative_inframe_insertion 10/10 ENST00000268489.10 NP_008816.3 Q15911-1Q8N2Y6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZFHX3ENST00000268489.10 linkc.10142_10165dupGGCAACTACAGCAGCAGCAGCAGC p.Arg3381_Gln3388dup conservative_inframe_insertion 10/101 NM_006885.4 ENSP00000268489.5 Q15911-1

Frequencies

GnomAD3 genomes
AF:
0.0000198
AC:
3
AN:
151352
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000194
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000296
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000125
AC:
3
AN:
240058
Hom.:
0
AF XY:
0.0000154
AC XY:
2
AN XY:
130176
show subpopulations
Gnomad AFR exome
AF:
0.0000657
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000185
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000124
AC:
18
AN:
1447894
Hom.:
0
Cov.:
34
AF XY:
0.0000125
AC XY:
9
AN XY:
719730
show subpopulations
Gnomad4 AFR exome
AF:
0.0000602
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000236
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000118
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.0000198
AC:
3
AN:
151352
Hom.:
0
Cov.:
32
AF XY:
0.0000406
AC XY:
3
AN XY:
73952
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000296
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs727502780; hg19: chr16-72822009; API