rs8055870

Variant names:

• chr16-72938191-A-G
• rs8055870
• NM_006885.4:c.3216+12278T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-72938191-A-G
• chr16-72938191-A-T

Variant summary

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

The NM_006885.4(ZFHX3):​c.3216+12278T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 152,278 control chromosomes in the GnomAD database, including 33,808 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 0.65 (33808 hom., cov: 35)
• Consequence: ZFHX3 NM_006885.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFHX3	NM_006885.4	c.3216+12278T>C		intron_variant	Intron 3 of 9	ENST00000268489.10	NP_008816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFHX3	ENST00000268489.10	c.3216+12278T>C		intron_variant	Intron 3 of 9	1	NM_006885.4	ENSP00000268489.5
ZFHX3	ENST00000397992.5	c.474+12278T>C		intron_variant	Intron 2 of 8	1		ENSP00000438926.3
ZFHX3	ENST00000641206.2	c.3216+12278T>C		intron_variant	Intron 11 of 17			ENSP00000493252.1

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98862 AN: 152160 Hom.: 33758 Cov.: 35

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.641

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

GnomAD4 genome AF: 0.650 AC: 98973 AN: 152278 Hom.: 33808 Cov.: 35 AF XY: 0.654 AC XY: 48698 AN XY: 74454

African (AFR) AF: 0.855 AC: 35537 AN: 41564

American (AMR) AF: 0.640 AC: 9801 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2151 AN: 3472

East Asian (EAS) AF: 0.775 AC: 4009 AN: 5174

South Asian (SAS) AF: 0.777 AC: 3755 AN: 4832

European-Finnish (FIN) AF: 0.539 AC: 5713 AN: 10600

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35871 AN: 68012

Other (OTH) AF: 0.642 AC: 1358 AN: 2116

Alfa AF: 0.581 Hom.: 89487

Bravo AF: 0.667

Asia WGS AF: 0.779 AC: 2703 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	2.5
DANN	Benign	0.66
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8055870; hg19: chr16-72972090;