X-48058745-G-A

Variant names:

• chrX-48058745-G-A
• rs1556908293
• NM_001282201.2:c.1697C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001282201.2(ZNF630):​c.1697C>T​(p.Thr566Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000128 in 1,094,190 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000013 (0 hom. 6 hem.)
• Consequence: ZNF630 NM_001282201.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.62
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18852526).
• BS2: High Hemizygotes in GnomAdExome4 at 6 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF630	NM_001282201.2	MANE Select	c.1697C>T	p.Thr566Ile	missense	Exon 5 of 5	NP_001269130.1	Q2M218-1
	ZNF630	NM_001037735.4		c.1697C>T	p.Thr566Ile	missense	Exon 5 of 5	NP_001032824.2	Q2M218-1
	ZNF630	NM_001190255.3		c.1655C>T	p.Thr552Ile	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.1697C>T	p.Thr566Ile	missense	Exon 5 of 5	ENSP00000354683.4	Q2M218-1
	ZNF630	ENST00000409324.7	TSL:1	c.1697C>T	p.Thr566Ile	missense	Exon 5 of 5	ENSP00000386393.3	Q2M218-1
	ZNF630	ENST00000871921.1		c.1697C>T	p.Thr566Ile	missense	Exon 5 of 5	ENSP00000541980.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000560 AC: 1 AN: 178684 AF XY: 0.0000157

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000126

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000128 AC: 14 AN: 1094190 Hom.: 0 Cov.: 31 AF XY: 0.0000167 AC XY: 6 AN XY: 359740

African (AFR) AF: 0.0000381 AC: 1 AN: 26217

American (AMR) AF: 0.00 AC: 0 AN: 35022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19296

East Asian (EAS) AF: 0.00 AC: 0 AN: 30127

South Asian (SAS) AF: 0.00 AC: 0 AN: 53855

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4076

European-Non Finnish (NFE) AF: 0.0000155 AC: 13 AN: 839302

Other (OTH) AF: 0.00 AC: 0 AN: 45937

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	0.65
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.6
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.062
Sift	Benign	0.070	T
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.16
MutPred		0.40		Loss of phosphorylation at T566 (P = 0.0312)
MVP		0.076
MPC		0.057
ClinPred		0.58	D
GERP RS		2.3
Varity_R		0.28
gMVP		0.023
Mutation Taster		=91/9	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

dbSNP: rs1556908293; hg19: chrX-47918134;