Variant 20-41185089-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001384324.1(ZHX3):c.2747C>T(p.Pro916Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,562,680 control chromosomes in the GnomAD database, including 20,414 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1709 hom., cov: 33)

Exomes 𝑓: 0.16 ( 18705 hom. )

Consequence

ZHX3
NM_001384324.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.06

Variant links:

Genes affected

ZHX3 (HGNC:15935): (zinc fingers and homeoboxes 3) This gene encodes a member of the zinc fingers and homeoboxes (ZHX) gene family. The encoded protein contains two C2H2-type zinc fingers and five homeodomains and forms a dimer with itself or with zinc fingers and homeoboxes family member 1. In the nucleus, the dimerized protein interacts with the A subunit of the ubiquitous transcription factor nuclear factor-Y and may function as a transcriptional repressor. [provided by RefSeq, Jul 2008]

ZHX3 links:

PLCG1 (HGNC:):

PLCG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042850673).

BP6

Variant 20-41185089-G-A is Benign according to our data. Variant chr20-41185089-G-A is described in ClinVar as [Benign]. Clinvar id is 1266725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZHX3	NM_001384317.1 linkuse as main transcript	c.*102C>T		3_prime_UTR_variant	4/4	ENST00000683867.1	NP_001371246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZHX3	ENST00000683867 linkuse as main transcript	c.*102C>T		3_prime_UTR_variant	4/4		NM_001384317.1	ENSP00000506788.1		Q9H4I2-1

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21170

AN:

152044

Hom.:

1709

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0958

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.00404

Gnomad SAS

AF:

0.0406

Gnomad FIN

AF:

0.250

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.140

GnomAD3 exomes

AF:

0.135

AC:

23557

AN:

174830

Hom.:

1909

AF XY:

0.130

AC XY:

12037

AN XY:

92476

show subpopulations

Gnomad AFR exome

AF:

0.0929

Gnomad AMR exome

AF:

0.132

Gnomad ASJ exome

AF:

0.142

Gnomad EAS exome

AF:

0.00355

Gnomad SAS exome

AF:

0.0441

Gnomad FIN exome

AF:

0.253

Gnomad NFE exome

AF:

0.168

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.156

AC:

220688

AN:

1410518

Hom.:

18705

Cov.:

AF XY:

0.154

AC XY:

107042

AN XY:

696664

show subpopulations

Gnomad4 AFR exome

AF:

0.0936

Gnomad4 AMR exome

AF:

0.133

Gnomad4 ASJ exome

AF:

0.146

Gnomad4 EAS exome

AF:

0.00622

Gnomad4 SAS exome

AF:

0.0436

Gnomad4 FIN exome

AF:

0.251

Gnomad4 NFE exome

AF:

0.170

Gnomad4 OTH exome

AF:

0.137

GnomAD4 genome

AF:

0.139

AC:

21180

AN:

152162

Hom.:

1709

Cov.:

AF XY:

0.139

AC XY:

10363

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0958

Gnomad4 AMR

AF:

0.125

Gnomad4 ASJ

AF:

0.136

Gnomad4 EAS

AF:

0.00405

Gnomad4 SAS

AF:

0.0408

Gnomad4 FIN

AF:

0.250

Gnomad4 NFE

AF:

0.169

Gnomad4 OTH

AF:

0.139

Alfa

AF:

0.158

Hom.:

2730

Bravo

AF:

0.129

TwinsUK

AF:

0.160

AC:

594

ALSPAC

AF:

0.166

AC:

641

ExAC

AF:

0.101

AC:

11802

Asia WGS

AF:

0.0330

AC:

116

AN:

3478

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	clinical testing	GeneDx	May 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.54

DANN

Benign

0.70

DEOGEN2

Benign

0.026

.;.;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.40

.;T;T;T

MetaRNN

Benign

0.0043

T;T;T;T

MetaSVM

Benign

-0.96

PROVEAN

Benign

-0.10

.;N;N;.

REVEL

Benign

0.0060

Sift

Benign

1.0

.;T;T;.

Sift4G

Benign

0.088

T;D;D;T

Vest4

0.051

ClinPred

0.0052

GERP RS

-9.5

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