rs12923103

Positions:

• chr16-73345035-A-G
• chr16-73345035-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386735.1(ZFHX3):​c.-807-26699T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 151,974 control chromosomes in the GnomAD database, including 39,666 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 0.72 (39666 hom., cov: 30)
• Consequence: ZFHX3 NM_001386735.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFHX3	NM_001386735.1	c.-807-26699T>C		intron_variant			NP_001373664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFHX3	ENST00000641206.2	c.-1290-26699T>C		intron_variant				ENSP00000493252	P1

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108891 AN: 151856 Hom.: 39617 Cov.: 30

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.732

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.717 AC: 108994 AN: 151974 Hom.: 39666 Cov.: 30 AF XY: 0.711 AC XY: 52791 AN XY: 74260

Gnomad4 AFR AF: 0.814

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.780

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.705

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.735

Alfa AF: 0.702 Hom.: 34924

Bravo AF: 0.712

Asia WGS AF: 0.605 AC: 2107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.065
DANN	Benign	0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12923103; hg19: chr16-73378934;