chrX-48058883-C-T

Variant names:

• chrX-48058883-C-T
• NM_001282201.2:c.1559G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001282201.2(ZNF630):​c.1559G>A​(p.Cys520Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ZNF630 NM_001282201.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56
• Publications: 0 publications found

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-AS1 (HGNC:41215): (ZNF630 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF630	NM_001282201.2	MANE Select	c.1559G>A	p.Cys520Tyr	missense	Exon 5 of 5	NP_001269130.1	Q2M218-1
	ZNF630	NM_001037735.4		c.1559G>A	p.Cys520Tyr	missense	Exon 5 of 5	NP_001032824.2	Q2M218-1
	ZNF630	NM_001190255.3		c.1517G>A	p.Cys506Tyr	missense	Exon 5 of 5	NP_001177184.1	Q2M218-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF630	ENST00000276054.9	TSL:1 MANE Select	c.1559G>A	p.Cys520Tyr	missense	Exon 5 of 5	ENSP00000354683.4	Q2M218-1
	ZNF630	ENST00000409324.7	TSL:1	c.1559G>A	p.Cys520Tyr	missense	Exon 5 of 5	ENSP00000386393.3	Q2M218-1
	ZNF630	ENST00000871921.1		c.1559G>A	p.Cys520Tyr	missense	Exon 5 of 5	ENSP00000541980.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0091	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Uncertain	0.052	D
MutationAssessor	Pathogenic	4.1	H
PhyloP100		2.6
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-10	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.17	B
Vest4		0.20
MutPred		0.84		Gain of ubiquitination at K522 (P = 0.0725)
MVP		0.33
MPC		0.035
ClinPred		1.0	D
GERP RS		1.4
Varity_R		0.76
gMVP		0.096
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

hg19: chrX-47918272;