X-48060168-T-C

Position:

• chrX-48060168-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001282201.2(ZNF630):​c.274A>G​(p.Ile92Val) 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: 21)
• Consequence: ZNF630 NM_001282201.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.283

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08447793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF630	NM_001282201.2	c.274A>G	p.Ile92Val	missense_variant	5/5	ENST00000276054.9	NP_001269130.1
ZNF630-AS1	NR_046742.2	n.123+3736T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF630	ENST00000276054.9	c.274A>G	p.Ile92Val	missense_variant	5/5	1	NM_001282201.2	ENSP00000354683	P1
ZNF630-AS1	ENST00000614448.1	n.123+3736T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 21

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

Oct 25, 2022

The c.274A>G (p.I92V) alteration is located in exon 5 (coding exon 4) of the ZNF630 gene. This alteration results from a A to G substitution at nucleotide position 274, causing the isoleucine (I) at amino acid position 92 to be replaced by a valine (V). 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	Benign	0.089
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0027	.;T;T;.;.
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.38	T;T;.;T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.084	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.90	.;L;L;.;.
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.49	.;.;N;.;N
REVEL	Benign	0.018
Sift	Benign	0.096	.;.;T;.;D
Sift4G	Benign	0.15	T;T;T;.;.
Polyphen		0.20	.;B;B;.;.
Vest4		0.10
MutPred		0.23		.;Loss of catalytic residue at L97 (P = 0.0295);Loss of catalytic residue at L97 (P = 0.0295);.;Loss of catalytic residue at L97 (P = 0.0295);
MVP		0.088
MPC		0.18
ClinPred		0.15	T
GERP RS		1.6
Varity_R		0.084
gMVP		0.018

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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-47919557;