chrX-48059641-C-G

Variant names:

• chrX-48059641-C-G
• rs1439183493
• NM_001282201.2:c.801G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001282201.2(ZNF630):​c.801G>C​(p.Met267Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000913 in 1,095,427 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: ZNF630 NM_001282201.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05517319).

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.801G>C	p.Met267Ile	missense	Exon 5 of 5	NP_001269130.1	Q2M218-1
	ZNF630	NM_001037735.4		c.801G>C	p.Met267Ile	missense	Exon 5 of 5	NP_001032824.2	Q2M218-1
	ZNF630	NM_001190255.3		c.759G>C	p.Met253Ile	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.801G>C	p.Met267Ile	missense	Exon 5 of 5	ENSP00000354683.4	Q2M218-1
	ZNF630	ENST00000409324.7	TSL:1	c.801G>C	p.Met267Ile	missense	Exon 5 of 5	ENSP00000386393.3	Q2M218-1
	ZNF630	ENST00000871921.1		c.801G>C	p.Met267Ile	missense	Exon 5 of 5	ENSP00000541980.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.13e-7 AC: 1 AN: 1095427 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 360855

African (AFR) AF: 0.00 AC: 0 AN: 26242

American (AMR) AF: 0.00 AC: 0 AN: 35145

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19322

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 54045

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40467

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 839930

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

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.84
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.046	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-2.6
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.030
Sift	Benign	0.082	T
Sift4G	Uncertain	0.022	D
Polyphen		0.0	B
Vest4		0.078
MutPred		0.54		Loss of MoRF binding (P = 0.0832)
MVP		0.13
MPC		0.027
ClinPred		0.037	T
GERP RS		0.25
Varity_R		0.16
gMVP		0.015
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: rs1439183493; hg19: chrX-47919030;