NM_001282201.2:c.1241G>A

Variant names:

• chrX-48059201-C-T
• rs202034946
• NM_001282201.2:c.1241G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001282201.2(ZNF630):​c.1241G>A​(p.Arg414Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000312 in 1,205,695 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 114 hemizygotes 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R414W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.00033 (0 hom. 112 hem.)
• Consequence: ZNF630 NM_001282201.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.32
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02998954).
• BS2: High Hemizygotes in GnomAd4 at 2 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.1241G>A	p.Arg414Gln	missense	Exon 5 of 5	NP_001269130.1	Q2M218-1
	ZNF630	NM_001037735.4		c.1241G>A	p.Arg414Gln	missense	Exon 5 of 5	NP_001032824.2	Q2M218-1
	ZNF630	NM_001190255.3		c.1199G>A	p.Arg400Gln	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.1241G>A	p.Arg414Gln	missense	Exon 5 of 5	ENSP00000354683.4	Q2M218-1
	ZNF630	ENST00000409324.7	TSL:1	c.1241G>A	p.Arg414Gln	missense	Exon 5 of 5	ENSP00000386393.3	Q2M218-1
	ZNF630	ENST00000871921.1		c.1241G>A	p.Arg414Gln	missense	Exon 5 of 5	ENSP00000541980.1

Frequencies

GnomAD3 genomes AF: 0.000154 AC: 17 AN: 110538 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000192

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: 0.000285

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000138 AC: 25 AN: 181700 AF XY: 0.000196

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000220

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000222

Gnomad OTH exome AF: 0.000223

GnomAD4 exome AF: 0.000328 AC: 359 AN: 1095157 Hom.: 0 Cov.: 35 AF XY: 0.000311 AC XY: 112 AN XY: 360615

African (AFR) AF: 0.00 AC: 0 AN: 26235

American (AMR) AF: 0.000228 AC: 8 AN: 35119

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

East Asian (EAS) AF: 0.0000332 AC: 1 AN: 30152

South Asian (SAS) AF: 0.00 AC: 0 AN: 54005

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40448

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

European-Non Finnish (NFE) AF: 0.000405 AC: 340 AN: 839784

Other (OTH) AF: 0.000217 AC: 10 AN: 45990

GnomAD4 genome AF: 0.000154 AC: 17 AN: 110538 Hom.: 0 Cov.: 23 AF XY: 0.0000604 AC XY: 2 AN XY: 33120

African (AFR) AF: 0.00 AC: 0 AN: 30208

American (AMR) AF: 0.000192 AC: 2 AN: 10428

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2638

East Asian (EAS) AF: 0.00 AC: 0 AN: 3488

South Asian (SAS) AF: 0.00 AC: 0 AN: 2664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 233

European-Non Finnish (NFE) AF: 0.000285 AC: 15 AN: 52712

Other (OTH) AF: 0.00 AC: 0 AN: 1486

Alfa AF: 0.000261 Hom.: 2

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000346 AC: 1

ExAC AF: 0.000157 AC: 19

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	Benign	0.20
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.81
DEOGEN2	Benign	0.0020	T
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.27	N
PhyloP100		-2.3
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.041
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.019	B
Vest4		0.039
MVP		0.15
MPC		0.028
ClinPred		0.029	T
GERP RS		-2.2
Varity_R		0.030
gMVP		0.021
Mutation Taster		=100/0	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: rs202034946; hg19: chrX-47918590; COSMIC: COSV52095348; COSMIC: COSV52095348;