rs9937546

Positions:

• chr16-72969820-T-C

Variant summary

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

The NM_006885.4(ZFHX3):​c.-49-9626A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,088 control chromosomes in the GnomAD database, including 8,751 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 0.33 (8751 hom., cov: 32)
• Consequence: ZFHX3 NM_006885.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFHX3	NM_006885.4	c.-49-9626A>G		intron_variant		ENST00000268489.10	NP_008816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFHX3	ENST00000268489.10	c.-49-9626A>G		intron_variant		1	NM_006885.4	ENSP00000268489	P1
ZFHX3	ENST00000397992.5	c.-23-18855A>G		intron_variant		1		ENSP00000438926
ZFHX3	ENST00000641206.2	c.-49-9626A>G		intron_variant				ENSP00000493252	P1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49910 AN: 151970 Hom.: 8728 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.0600

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.329 AC: 49973 AN: 152088 Hom.: 8751 Cov.: 32 AF XY: 0.323 AC XY: 24024 AN XY: 74352

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.0602

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.290

Alfa AF: 0.321 Hom.: 8247

Bravo AF: 0.317

Asia WGS AF: 0.139 AC: 488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs9937546; hg19: chr16-73003719;