Genetic Variant ZHX2:c.*1172A>G (chr8-122974409-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_014943.5(ZHX2):c.*1172A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,570 control chromosomes in the GnomAD database, including 20,862 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 0.51 ( 20850 hom., cov: 29)

Exomes 𝑓: 0.35 ( 12 hom. )

Consequence

ZHX2
NM_014943.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.76

Publications

22 publications found

Variant links:

Genes affected

ZHX2 (HGNC:18513): (zinc fingers and homeoboxes 2) The members of the zinc fingers and homeoboxes gene family are nuclear homodimeric transcriptional repressors that interact with the A subunit of nuclear factor-Y (NF-YA) and contain two C2H2-type zinc fingers and five homeobox DNA-binding domains. This gene encodes member 2 of this gene family. In addition to forming homodimers, this protein heterodimerizes with member 1 of the zinc fingers and homeoboxes family. [provided by RefSeq, Jul 2008]

ZHX2 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZHX2	NM_014943.5 link	c.*1172A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000314393.6	NP_055758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZHX2	ENST00000314393.6 link	c.*1172A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_014943.5	ENSP00000314709.4

Frequencies

GnomAD3 genomes

AF:

0.511

AC:

77225

AN:

151152

Hom.:

20809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.688

Gnomad AMI

AF:

0.557

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.487

Gnomad EAS

AF:

0.279

Gnomad SAS

AF:

0.524

Gnomad FIN

AF:

0.379

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.446

Gnomad OTH

AF:

0.514

GnomAD4 exome

AF:

0.350

AC:

105

AN:

300

Hom.:

Cov.:

AF XY:

0.337

AC XY:

AN XY:

184

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.351

AC:

101

AN:

288

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.511

AC:

77325

AN:

151270

Hom.:

20850

Cov.:

AF XY:

0.507

AC XY:

37429

AN XY:

73848

show subpopulations

African (AFR)

AF:

0.688

AC:

28355

AN:

41184

American (AMR)

AF:

0.485

AC:

7379

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.487

AC:

1685

AN:

3462

East Asian (EAS)

AF:

0.280

AC:

1431

AN:

5118

South Asian (SAS)

AF:

0.523

AC:

2483

AN:

4750

European-Finnish (FIN)

AF:

0.379

AC:

3965

AN:

10452

Middle Eastern (MID)

AF:

0.578

AC:

170

AN:

294

European-Non Finnish (NFE)

AF:

0.446

AC:

30268

AN:

67792

Other (OTH)

AF:

0.518

AC:

1083

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

1696

3392

5088

6784

8480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

666

1332

1998

2664

3330

<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:

0.473

Hom.:

22769

Bravo

AF:

0.521

Asia WGS

AF:

0.439

AC:

1528

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.61

PhyloP100

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over