X-48059611-C-G

Position:

• chrX-48059611-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001282201.2(ZNF630):​c.831G>C​(p.Gln277His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: ZNF630 NM_001282201.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.92

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058747143).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF630	NM_001282201.2	c.831G>C	p.Gln277His	missense_variant	5/5	ENST00000276054.9	NP_001269130.1
ZNF630-AS1	NR_046742.2	n.123+3179C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF630	ENST00000276054.9	c.831G>C	p.Gln277His	missense_variant	5/5	1	NM_001282201.2	ENSP00000354683	P1
ZNF630-AS1	ENST00000614448.1	n.123+3179C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2023

The c.831G>C (p.Q277H) alteration is located in exon 5 (coding exon 4) of the ZNF630 gene. This alteration results from a G to C substitution at nucleotide position 831, causing the glutamine (Q) at amino acid position 277 to be replaced by a histidine (H). 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	Uncertain	0.41
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.94
CADD	Benign	8.3
DANN	Benign	0.79
DEOGEN2	Benign	0.0026	.;T;T;.
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.20	T;T;.;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.059	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.35	.;N;N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.79	.;.;N;N
REVEL	Benign	0.015
Sift	Benign	1.0	.;.;T;T
Sift4G	Benign	0.66	T;T;T;T
Polyphen		0.14	.;B;B;.
Vest4		0.057
MutPred		0.34		.;Loss of solvent accessibility (P = 0.0635);Loss of solvent accessibility (P = 0.0635);.;
MVP		0.014
MPC		0.026
ClinPred		0.089	T
GERP RS		0.015
Varity_R		0.11
gMVP		0.031

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-47919000;