rs727502780

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP3BP6BS1BS2

The NM_006885.4(ZFHX3):c.10142_10165delGGCAACTACAGCAGCAGCAGCAGC(p.Arg3381_Gln3388del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000444 in 1,599,342 control chromosomes in the GnomAD database, including 3 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 3 hom. )

Consequence

ZFHX3
NM_006885.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1B:1

Conservation

PhyloP100: 7.12

Publications

3 publications found

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:

ZFHX3-AS1 (HGNC:56033): (ZFHX3 antisense RNA 1)

ZFHX3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_006885.4

BP6

Variant 16-72788110-TGCTGCTGCTGCTGCTGTAGTTGCC-T is Benign according to our data. Variant chr16-72788110-TGCTGCTGCTGCTGCTGTAGTTGCC-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 18167.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000363 (55/151470) while in subpopulation SAS AF = 0.00229 (11/4794). AF 95% confidence interval is 0.00129. There are 0 homozygotes in GnomAd4. There are 26 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFHX3	NM_006885.4 link	c.10142_10165delGGCAACTACAGCAGCAGCAGCAGC	p.Arg3381_Gln3388del	disruptive_inframe_deletion	Exon 10 of 10	ENST00000268489.10	NP_008816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFHX3	ENST00000268489.10 link	c.10142_10165delGGCAACTACAGCAGCAGCAGCAGC	p.Arg3381_Gln3388del	disruptive_inframe_deletion	Exon 10 of 10	1	NM_006885.4	ENSP00000268489.5

Frequencies

GnomAD3 genomes

AF:

0.000363

AC:

AN:

151352

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000330

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000389

Gnomad SAS

AF:

0.00229

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000399

Gnomad OTH

AF:

0.000481

GnomAD2 exomes

AF:

0.000558

AC:

134

AN:

240058

AF XY:

0.000668

show subpopulations

Gnomad AFR exome

AF:

0.0000657

Gnomad AMR exome

AF:

0.000206

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000499

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000462

Gnomad OTH exome

AF:

0.000846

GnomAD4 exome

AF:

0.000452

AC:

655

AN:

1447872

Hom.:

AF XY:

0.000520

AC XY:

374

AN XY:

719724

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33248

American (AMR)

AF:

0.000250

AC:

AN:

43990

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25822

East Asian (EAS)

AF:

0.00109

AC:

AN:

39476

South Asian (SAS)

AF:

0.00243

AC:

206

AN:

84906

European-Finnish (FIN)

AF:

0.0000199

AC:

AN:

50270

Middle Eastern (MID)

AF:

0.00210

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.000305

AC:

337

AN:

1104522

Other (OTH)

AF:

0.000651

AC:

AN:

59922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

121

162

202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000363

AC:

AN:

151470

Hom.:

Cov.:

AF XY:

0.000351

AC XY:

AN XY:

74080

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41346

American (AMR)

AF:

0.000329

AC:

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.000390

AC:

AN:

5132

South Asian (SAS)

AF:

0.00229

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000399

AC:

AN:

67662

Other (OTH)

AF:

0.000476

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000287

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Prostate cancer, somatic

Pathogenic:1

Apr 01, 2005

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not provided

Uncertain:1

Feb 01, 2017

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

May 04, 2022

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

7.1

Mutation Taster

=72/128

disease causing (long InDel)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over