Genetic Variant NM_001282201.2:c.801G>A (chrX-48059641-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001282201.2(ZNF630):c.801G>A(p.Met267Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000896 in 111,666 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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 0.0000090 ( 0 hom., 0 hem., cov: 22)

Consequence

ZNF630
NM_001282201.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.64

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06687972).

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.801G>A	p.Met267Ile	missense	Exon 5 of 5	NP_001269130.1	Q2M218-1
ZNF630	NM_001037735.4		c.801G>A	p.Met267Ile	missense	Exon 5 of 5	NP_001032824.2	Q2M218-1
ZNF630	NM_001190255.3		c.759G>A	p.Met253Ile	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.801G>A	p.Met267Ile	missense	Exon 5 of 5	ENSP00000354683.4	Q2M218-1
ZNF630	ENST00000409324.7	TSL:1	c.801G>A	p.Met267Ile	missense	Exon 5 of 5	ENSP00000386393.3	Q2M218-1
ZNF630	ENST00000871921.1		c.801G>A	p.Met267Ile	missense	Exon 5 of 5	ENSP00000541980.1

Frequencies

GnomAD3 genomes

AF:

0.00000896

AC:

AN:

111666

Hom.:

Cov.:

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000896

AC:

AN:

111666

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33960

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30598

American (AMR)

AF:

0.00

AC:

AN:

10511

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2644

East Asian (EAS)

AF:

0.00

AC:

AN:

3553

South Asian (SAS)

AF:

0.00

AC:

AN:

2705

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6096

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53121

Other (OTH)

AF:

0.00

AC:

AN:

1513

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

0.14

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.7

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.011

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.046

M_CAP

Benign

0.0012

MetaRNN

Benign

0.067

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.34

PhyloP100

-2.6

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.97

REVEL

Benign

0.038

Sift

Benign

0.082

Sift4G

Uncertain

0.022

Polyphen

0.0

Vest4

0.078

MutPred

0.54

Loss of MoRF binding (P = 0.0832)

MVP

0.13

MPC

0.027

ClinPred

0.046

GERP RS

0.25

Varity_R

0.16

gMVP

0.015

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over