Variant X-24179316-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_003410.4(ZFX):c.192C>A(p.Ile64Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00699 in 1,210,160 control chromosomes in the GnomAD database, including 42 homozygotes. There are 2,709 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 2 hom., 165 hem., cov: 22)

Exomes 𝑓: 0.0071 ( 40 hom. 2544 hem. )

Consequence

ZFX
NM_003410.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.96

Variant links:

Genes affected

ZFX (HGNC:12869): (zinc finger protein X-linked) This gene on the X chromosome is structurally similar to a related gene on the Y chromosome. It encodes a member of the krueppel C2H2-type zinc-finger protein family. The full-length protein contains an acidic transcriptional activation domain (AD), a nuclear localization sequence (NLS) and a DNA binding domain (DBD) consisting of 13 C2H2-type zinc fingers. Studies in mouse embryonic and adult hematopoietic stem cells showed that this gene was required as a transcriptional regulator for self-renewal of both stem cell types, but it was dispensable for growth and differentiation of their progeny. Multiple alternatively spliced transcript variants encoding different isoforms have been identified, but the full-length nature of some variants has not been determined. [provided by RefSeq, May 2010]

ZFX links:

ZFX (HGNC:):

ZFX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant X-24179316-C-A is Benign according to our data. Variant chrX-24179316-C-A is described in ClinVar as [Benign]. Clinvar id is 711679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.96 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFX	NM_003410.4 linkuse as main transcript	c.192C>A	p.Ile64Ile	synonymous_variant	5/10	ENST00000304543.10	NP_003401.2	P17010-1A0A024RC04Q8WXB7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFX	ENST00000304543.10 linkuse as main transcript	c.192C>A	p.Ile64Ile	synonymous_variant	5/10	5	NM_003410.4	ENSP00000304985.5		P17010-1

Frequencies

GnomAD3 genomes

AF:

0.00567

AC:

635

AN:

111932

Hom.:

Cov.:

AF XY:

0.00484

AC XY:

165

AN XY:

34122

show subpopulations

Gnomad AFR

AF:

0.000975

Gnomad AMI

AF:

0.0456

Gnomad AMR

AF:

0.00256

Gnomad ASJ

AF:

0.0618

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000369

Gnomad FIN

AF:

0.000498

Gnomad MID

AF:

0.00840

Gnomad NFE

AF:

0.00688

Gnomad OTH

AF:

0.00730

GnomAD3 exomes

AF:

0.00640

AC:

1174

AN:

183482

Hom.:

AF XY:

0.00604

AC XY:

410

AN XY:

67926

show subpopulations

Gnomad AFR exome

AF:

0.000456

Gnomad AMR exome

AF:

0.00339

Gnomad ASJ exome

AF:

0.0641

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000524

Gnomad FIN exome

AF:

0.000437

Gnomad NFE exome

AF:

0.00660

Gnomad OTH exome

AF:

0.00817

GnomAD4 exome

AF:

0.00713

AC:

7825

AN:

1098177

Hom.:

Cov.:

AF XY:

0.00700

AC XY:

2544

AN XY:

363535

show subpopulations

Gnomad4 AFR exome

AF:

0.000606

Gnomad4 AMR exome

AF:

0.00364

Gnomad4 ASJ exome

AF:

0.0620

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000462

Gnomad4 FIN exome

AF:

0.000790

Gnomad4 NFE exome

AF:

0.00712

Gnomad4 OTH exome

AF:

0.00876

GnomAD4 genome

AF:

0.00566

AC:

634

AN:

111983

Hom.:

Cov.:

AF XY:

0.00483

AC XY:

165

AN XY:

34183

show subpopulations

Gnomad4 AFR

AF:

0.000973

Gnomad4 AMR

AF:

0.00256

Gnomad4 ASJ

AF:

0.0618

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000370

Gnomad4 FIN

AF:

0.000498

Gnomad4 NFE

AF:

0.00688

Gnomad4 OTH

AF:

0.00721

Alfa

AF:

0.0137

Hom.:

111

Bravo

AF:

0.00587

EpiCase

AF:

0.00736

EpiControl

AF:

0.00859

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	May 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

8.0

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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