rs764255

Positions:

• chr16-73679784-C-T

Variant summary

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

The NM_001386735.1(ZFHX3):​c.-1064+396G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 152,010 control chromosomes in the GnomAD database, including 25,797 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 0.57 (25797 hom., cov: 32)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: ZFHX3 NM_001386735.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFHX3	NM_001386735.1	c.-1064+396G>A		intron_variant			NP_001373664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFHX3	ENST00000641206.2	c.-1547+396G>A		intron_variant				ENSP00000493252.1
ZFHX3	ENST00000641018.1	n.557G>A		non_coding_transcript_exon_variant	2/2
ZFHX3	ENST00000642085.1	n.163+396G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86243 AN: 151886 Hom.: 25798 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.602

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 NFE exome AF: 0.333

GnomAD4 genome AF: 0.567 AC: 86262 AN: 152004 Hom.: 25797 Cov.: 32 AF XY: 0.569 AC XY: 42275 AN XY: 74308

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.784

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.607

Alfa AF: 0.635 Hom.: 50604

Bravo AF: 0.569

Asia WGS AF: 0.687 AC: 2390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs764255; hg19: chr16-73713683;