Genetic Variant ZNF630:p.Gly476Ser (chrX-48059016-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001282201.2(ZNF630):c.1426G>A(p.Gly476Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000454 in 1,205,454 control chromosomes in the GnomAD database, including 7 homozygotes. There are 167 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., 8 hem., cov: 22)

Exomes 𝑓: 0.00047 ( 7 hom. 159 hem. )

Consequence

ZNF630
NM_001282201.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.92

Publications

0 publications found

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:41215): (ZNF630 antisense RNA 1)

ZNF630-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029240996).

BS2

High Hemizygotes in GnomAd4 at 8 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282201.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF630	NM_001282201.2	MANE Select	c.1426G>A	p.Gly476Ser	missense	Exon 5 of 5	NP_001269130.1	Q2M218-1
ZNF630	NM_001037735.4		c.1426G>A	p.Gly476Ser	missense	Exon 5 of 5	NP_001032824.2	Q2M218-1
ZNF630	NM_001190255.3		c.1384G>A	p.Gly462Ser	missense	Exon 5 of 5	NP_001177184.1	Q2M218-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF630	ENST00000276054.9	TSL:1 MANE Select	c.1426G>A	p.Gly476Ser	missense	Exon 5 of 5	ENSP00000354683.4	Q2M218-1
ZNF630	ENST00000409324.7	TSL:1	c.1426G>A	p.Gly476Ser	missense	Exon 5 of 5	ENSP00000386393.3	Q2M218-1
ZNF630	ENST00000871921.1		c.1426G>A	p.Gly476Ser	missense	Exon 5 of 5	ENSP00000541980.1

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

110189

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000332

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000965

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:

0.000475

Gnomad OTH

AF:

0.00135

GnomAD2 exomes

AF:

0.000181

AC:

AN:

182100

AF XY:

0.000180

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000370

Gnomad OTH exome

AF:

0.000445

GnomAD4 exome

AF:

0.000473

AC:

518

AN:

1095210

Hom.:

Cov.:

AF XY:

0.000441

AC XY:

159

AN XY:

360676

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26238

American (AMR)

AF:

0.000114

AC:

AN:

35142

Ashkenazi Jewish (ASJ)

AF:

0.000104

AC:

AN:

19309

East Asian (EAS)

AF:

0.00

AC:

AN:

30155

South Asian (SAS)

AF:

0.00

AC:

AN:

54024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40422

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4128

European-Non Finnish (NFE)

AF:

0.000586

AC:

492

AN:

839808

Other (OTH)

AF:

0.000435

AC:

AN:

45984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000263

AC:

AN:

110244

Hom.:

Cov.:

AF XY:

0.000244

AC XY:

AN XY:

32844

show subpopulations

African (AFR)

AF:

0.0000331

AC:

AN:

30213

American (AMR)

AF:

0.0000964

AC:

AN:

10377

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2616

East Asian (EAS)

AF:

0.00

AC:

AN:

3482

South Asian (SAS)

AF:

0.00

AC:

AN:

2598

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5947

Middle Eastern (MID)

AF:

0.00

AC:

AN:

212

European-Non Finnish (NFE)

AF:

0.000475

AC:

AN:

52626

Other (OTH)

AF:

0.00134

AC:

AN:

1498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000504

Hom.:

Bravo

AF:

0.000295

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00173

AC:

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.000492

EpiControl

AF:

0.000358

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.92

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0022

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.47

M_CAP

Benign

0.0015

MetaRNN

Benign

0.029

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.24

PhyloP100

-1.9

PrimateAI

Benign

0.38

PROVEAN

Benign

0.93

REVEL

Benign

0.076

Sift

Benign

0.87

Sift4G

Benign

0.73

Polyphen

0.95

Vest4

0.081

MVP

0.13

MPC

0.21

ClinPred

0.10

GERP RS

1.4

Varity_R

0.093

gMVP

0.020

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over