X-48058883-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF630	NM_001282201.2	c.1559G>A	p.Cys520Tyr	missense_variant	Exon 5 of 5	ENST00000276054.9	NP_001269130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF630	ENST00000276054.9	c.1559G>A	p.Cys520Tyr	missense_variant	Exon 5 of 5	1	NM_001282201.2	ENSP00000354683.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 23, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1559G>A (p.C520Y) alteration is located in exon 5 (coding exon 4) of the ZNF630 gene. This alteration results from a G to A substitution at nucleotide position 1559, causing the cysteine (C) at amino acid position 520 to be replaced by a tyrosine (Y). 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	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;T;.
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.29	T;T;.;T
M_CAP	Benign	0.0091	T
MetaRNN	Uncertain	0.61	D;D;D;D
MetaSVM	Uncertain	0.052	D
MutationAssessor	Pathogenic	4.1	.;H;H;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-10	.;.;D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	.;.;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.17	.;B;B;.
Vest4		0.20
MutPred		0.84		.;Gain of ubiquitination at K522 (P = 0.0725);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-47918272;