Variant 16-72957387-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006885.4(ZFHX3):c.2719+40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 1,552,348 control chromosomes in the GnomAD database, including 343,153 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 0.62 ( 29617 hom., cov: 31)

Exomes 𝑓: 0.66 ( 313536 hom. )

Consequence

ZFHX3
NM_006885.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.314

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFHX3	NM_006885.4 linkuse as main transcript	c.2719+40G>A		intron_variant		ENST00000268489.10	NP_008816.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ZFHX3	ENST00000268489.10 linkuse as main transcript	c.2719+40G>A	intron_variant	1	NM_006885.4	ENSP00000268489	P1	Q15911-1
ZFHX3	ENST00000397992.5 linkuse as main transcript	c.-23-6422G>A	intron_variant	1		ENSP00000438926		Q15911-2
ZFHX3	ENST00000641206.2 linkuse as main transcript	c.2719+40G>A	intron_variant			ENSP00000493252	P1	Q15911-1

Frequencies

GnomAD3 genomes

AF:

0.615

AC:

93516

AN:

151944

Hom.:

29609

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.666

Gnomad AMR

AF:

0.582

Gnomad ASJ

AF:

0.578

Gnomad EAS

AF:

0.447

Gnomad SAS

AF:

0.466

Gnomad FIN

AF:

0.770

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.697

Gnomad OTH

AF:

0.615

GnomAD3 exomes

AF:

0.616

AC:

126940

AN:

206072

Hom.:

40622

AF XY:

0.621

AC XY:

67822

AN XY:

109254

show subpopulations

Gnomad AFR exome

AF:

0.485

Gnomad AMR exome

AF:

0.508

Gnomad ASJ exome

AF:

0.579

Gnomad EAS exome

AF:

0.455

Gnomad SAS exome

AF:

0.468

Gnomad FIN exome

AF:

0.777

Gnomad NFE exome

AF:

0.699

Gnomad OTH exome

AF:

0.639

GnomAD4 exome

AF:

0.664

AC:

929671

AN:

1400288

Hom.:

313536

Cov.:

AF XY:

0.660

AC XY:

455040

AN XY:

689064

show subpopulations

Gnomad4 AFR exome

AF:

0.486

Gnomad4 AMR exome

AF:

0.515

Gnomad4 ASJ exome

AF:

0.577

Gnomad4 EAS exome

AF:

0.435

Gnomad4 SAS exome

AF:

0.481

Gnomad4 FIN exome

AF:

0.769

Gnomad4 NFE exome

AF:

0.694

Gnomad4 OTH exome

AF:

0.643

GnomAD4 genome

AF:

0.615

AC:

93576

AN:

152060

Hom.:

29617

Cov.:

AF XY:

0.615

AC XY:

45724

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.496

Gnomad4 AMR

AF:

0.582

Gnomad4 ASJ

AF:

0.578

Gnomad4 EAS

AF:

0.446

Gnomad4 SAS

AF:

0.468

Gnomad4 FIN

AF:

0.770

Gnomad4 NFE

AF:

0.697

Gnomad4 OTH

AF:

0.611

Alfa

AF:

0.666

Hom.:

46890

Bravo

AF:

0.595

Asia WGS

AF:

0.470

AC:

1637

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.3

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over