Variant X-48059792-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001282201.2(ZNF630):c.650C>T(p.Ala217Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,206,885 control chromosomes in the GnomAD database, including 2 homozygotes. There are 49 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.00013 ( 2 hom. 47 hem. )

Consequence

ZNF630
NM_001282201.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: -1.92

Variant links:

Genes affected

ZNF630 (HGNC:28855): (zinc finger protein 630) This gene encodes a protein containing an N-terminal Kruppel-associated box-containing (KRAB) domain and 13 Kruppel-type C2H2 zinc finger domains. This gene resides on an area of chromosome X that has been implicated in nonsyndromic X-linked cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ZNF630 links:

ZNF630-AS1 (HGNC:):

ZNF630-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.057047814).

BP6

Variant X-48059792-G-A is Benign according to our data. Variant chrX-48059792-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1206405.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-48059792-G-A is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF630	NM_001282201.2 linkuse as main transcript	c.650C>T	p.Ala217Val	missense_variant	5/5	ENST00000276054.9	NP_001269130.1	Q2M218-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF630	ENST00000276054.9 linkuse as main transcript	c.650C>T	p.Ala217Val	missense_variant	5/5	1	NM_001282201.2	ENSP00000354683.4		Q2M218-1

Frequencies

GnomAD3 genomes

AF:

0.000117

AC:

AN:

111444

Hom.:

Cov.:

AF XY:

0.0000592

AC XY:

AN XY:

33764

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000245

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000985

AC:

AN:

182805

Hom.:

AF XY:

0.000119

AC XY:

AN XY:

67313

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000221

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000132

AC:

145

AN:

1095441

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

360861

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000741

Gnomad4 NFE exome

AF:

0.000167

Gnomad4 OTH exome

AF:

0.0000435

GnomAD4 genome

AF:

0.000117

AC:

AN:

111444

Hom.:

Cov.:

AF XY:

0.0000592

AC XY:

AN XY:

33764

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000245

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000151

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000298

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000328

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.091

DANN

Benign

0.75

DEOGEN2

Benign

0.0066

.;T;T;.

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.14

T;T;.;T

M_CAP

Benign

0.00066

MetaRNN

Benign

0.057

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.7

.;L;L;.

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.69

.;.;N;N

REVEL

Benign

0.032

Sift

Benign

0.17

.;.;T;D

Sift4G

Benign

0.36

T;T;T;T

Polyphen

0.0

.;B;B;.

Vest4

0.017

MVP

0.10

MPC

0.026

ClinPred

0.055

GERP RS

-4.9

Varity_R

0.052

gMVP

0.026

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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