NM_001282201.2:c.1296G>T

Variant names:

• chrX-48059146-C-A
• rs374904933
• NM_001282201.2:c.1296G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001282201.2(ZNF630):​c.1296G>T​(p.Lys432Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000332 in 1,206,521 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 0.000018 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: ZNF630 NM_001282201.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.01
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07736617).

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.1296G>T	p.Lys432Asn	missense	Exon 5 of 5	NP_001269130.1	Q2M218-1
	ZNF630	NM_001037735.4		c.1296G>T	p.Lys432Asn	missense	Exon 5 of 5	NP_001032824.2	Q2M218-1
	ZNF630	NM_001190255.3		c.1254G>T	p.Lys418Asn	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.1296G>T	p.Lys432Asn	missense	Exon 5 of 5	ENSP00000354683.4	Q2M218-1
	ZNF630	ENST00000409324.7	TSL:1	c.1296G>T	p.Lys432Asn	missense	Exon 5 of 5	ENSP00000386393.3	Q2M218-1
	ZNF630	ENST00000871921.1		c.1296G>T	p.Lys432Asn	missense	Exon 5 of 5	ENSP00000541980.1

Frequencies

GnomAD3 genomes AF: 0.0000180 AC: 2 AN: 111171 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000657

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000549 AC: 1 AN: 182148 AF XY: 0.00

Gnomad AFR exome AF: 0.0000766

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000183 AC: 2 AN: 1095350 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 360778

African (AFR) AF: 0.0000762 AC: 2 AN: 26239

American (AMR) AF: 0.00 AC: 0 AN: 35133

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19317

East Asian (EAS) AF: 0.00 AC: 0 AN: 30155

South Asian (SAS) AF: 0.00 AC: 0 AN: 54029

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40453

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4128

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 839905

Other (OTH) AF: 0.00 AC: 0 AN: 45991

GnomAD4 genome AF: 0.0000180 AC: 2 AN: 111171 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33535

African (AFR) AF: 0.0000657 AC: 2 AN: 30457

American (AMR) AF: 0.00 AC: 0 AN: 10453

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2632

East Asian (EAS) AF: 0.00 AC: 0 AN: 3533

South Asian (SAS) AF: 0.00 AC: 0 AN: 2653

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 235

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52951

Other (OTH) AF: 0.00 AC: 0 AN: 1504

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000826 AC: 1

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	Uncertain	0.39
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	10
DANN	Benign	0.88
DEOGEN2	Benign	0.012	T
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.91	L
PhyloP100		-2.0
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.047
Sift	Benign	0.45	T
Sift4G	Benign	0.26	T
Polyphen		0.20	B
Vest4		0.14
MutPred		0.30		Loss of methylation at K432 (P = 0)
MVP		0.33
MPC		0.18
ClinPred		0.039	T
GERP RS		-1.6
Varity_R		0.23
gMVP		0.012
Mutation Taster		=99/1	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: rs374904933; hg19: chrX-47918535;