rs899884

Variant names:

• chr16-73690389-A-C
• rs899884
• NM_001386735.1:c.-1124-10149T>G

Your query was ambiguous. Multiple possible variants found:

• chr16-73690389-A-C
• chr16-73690389-A-G
• chr16-73690389-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386735.1(ZFHX3):​c.-1124-10149T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 152,190 control chromosomes in the GnomAD database, including 61,632 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 0.89 (61632 hom., cov: 32)
• Consequence: ZFHX3 NM_001386735.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• syndromic complex neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: Broad Center for Mendelian Genomics
• spinocerebellar ataxia type 4

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• epilepsy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386735.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFHX3	NM_001386735.1		c.-1124-10149T>G		intron	N/A	NP_001373664.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFHX3	ENST00000641206.2		c.-1607-10149T>G		intron	N/A	ENSP00000493252.1
	ZFHX3	ENST00000641018.1		n.101-10149T>G		intron	N/A
	ZFHX3	ENST00000642085.1		n.103-10149T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135596 AN: 152072 Hom.: 61596 Cov.: 32

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.972

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.985

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.965

Gnomad OTH AF: 0.904

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

GnomAD4 genome AF: 0.892 AC: 135686 AN: 152190 Hom.: 61632 Cov.: 32 AF XY: 0.894 AC XY: 66518 AN XY: 74414

African (AFR) AF: 0.702 AC: 29095 AN: 41470

American (AMR) AF: 0.942 AC: 14399 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.972 AC: 3375 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5153 AN: 5170

South Asian (SAS) AF: 0.924 AC: 4463 AN: 4828

European-Finnish (FIN) AF: 0.985 AC: 10462 AN: 10616

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.965 AC: 65665 AN: 68028

Other (OTH) AF: 0.905 AC: 1910 AN: 2110

Alfa AF: 0.933 Hom.: 43018

Bravo AF: 0.881

Asia WGS AF: 0.931 AC: 3238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.47
PhyloP100		-0.23

Splicing

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

Other links and lift over

dbSNP: rs899884; hg19: chr16-73724288;