Variant 8-122952515-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_014943.5(ZHX2):c.1005C>T(p.Asn335=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,614,170 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0025 ( 13 hom. )

Consequence

ZHX2
NM_014943.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.840

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 8-122952515-C-T is Benign according to our data. Variant chr8-122952515-C-T is described in ClinVar as [Benign]. Clinvar id is 716977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.84 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00693 (1055/152296) while in subpopulation AFR AF= 0.0186 (775/41566). AF 95% confidence interval is 0.0176. There are 5 homozygotes in gnomad4. There are 500 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZHX2	NM_014943.5 linkuse as main transcript	c.1005C>T	p.Asn335=	synonymous_variant	3/4	ENST00000314393.6	NP_055758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZHX2	ENST00000314393.6 linkuse as main transcript	c.1005C>T	p.Asn335=	synonymous_variant	3/4	1	NM_014943.5	ENSP00000314709	P1

Frequencies

GnomAD3 genomes

AF:

0.00693

AC:

1055

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0187

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00266

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00332

AC:

834

AN:

251390

Hom.:

AF XY:

0.00290

AC XY:

394

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.0185

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.00357

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00291

Gnomad NFE exome

AF:

0.00278

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00253

AC:

3698

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00247

AC XY:

1796

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0188

Gnomad4 AMR exome

AF:

0.00264

Gnomad4 ASJ exome

AF:

0.00440

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.00292

Gnomad4 NFE exome

AF:

0.00224

Gnomad4 OTH exome

AF:

0.00257

GnomAD4 genome

AF:

0.00693

AC:

1055

AN:

152296

Hom.:

Cov.:

AF XY:

0.00671

AC XY:

500

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0186

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.00266

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00456

Hom.:

Bravo

AF:

0.00729

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00191

EpiControl

AF:

0.00160

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.42

DANN

Benign

0.72

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over