Variant X-48059868-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001282201.2(ZNF630):c.574C>A(p.Leu192Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000614 in 1,206,024 control chromosomes in the GnomAD database, including 1 homozygotes. There are 21 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000067 ( 1 hom. 21 hem. )

Consequence

ZNF630
NM_001282201.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.962

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0444341).

BS2

High Hemizygotes in GnomAdExome4 at 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF630	NM_001282201.2 linkuse as main transcript	c.574C>A	p.Leu192Ile	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.574C>A	p.Leu192Ile	missense_variant	5/5	1	NM_001282201.2	ENSP00000354683.4		Q2M218-1

Frequencies

GnomAD3 genomes

AF:

0.00000902

AC:

AN:

110902

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33264

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:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000165

AC:

AN:

182128

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

66776

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:

0.0000369

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000667

AC:

AN:

1095122

Hom.:

Cov.:

AF XY:

0.0000582

AC XY:

AN XY:

360572

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000332

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000834

Gnomad4 OTH exome

AF:

0.0000435

GnomAD4 genome

AF:

0.00000902

AC:

AN:

110902

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33264

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:

0.0000189

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000435

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 25, 2024

The c.574C>A (p.L192I) alteration is located in exon 5 (coding exon 4) of the ZNF630 gene. This alteration results from a C to A substitution at nucleotide position 574, causing the leucine (L) at amino acid position 192 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.6

DANN

Benign

0.97

DEOGEN2

Benign

0.0034

.;T;T;.;.;.

FATHMM_MKL

Benign

0.0075

LIST_S2

Benign

0.0065

T;T;.;T;T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.044

T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.47

.;N;N;.;.;.

PrimateAI

Benign

0.35

PROVEAN

Benign

0.19

.;.;N;N;.;N

REVEL

Benign

0.022

Sift

Benign

0.40

.;.;T;T;.;T

Sift4G

Benign

0.56

T;T;T;T;.;.

Polyphen

0.28

.;B;B;.;.;.

Vest4

0.069

MutPred

0.20

.;Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);.;.;Gain of helix (P = 0.0696);

MVP

0.081

MPC

0.029

ClinPred

0.045

GERP RS

0.19

Varity_R

0.082

gMVP

0.017

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