chrX-48058872-A-T

Position:

• chrX-48058872-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001282201.2(ZNF630):​c.1570T>A​(p.Phe524Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000365 in 1,094,863 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000037 (0 hom. 2 hem.)
• Consequence: ZNF630 NM_001282201.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.97

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:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF630	NM_001282201.2	c.1570T>A	p.Phe524Ile	missense_variant	5/5	ENST00000276054.9	NP_001269130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF630	ENST00000276054.9	c.1570T>A	p.Phe524Ile	missense_variant	5/5	1	NM_001282201.2	ENSP00000354683.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.0000166 AC: 3 AN: 180532 Hom.: 0 AF XY: 0.0000153 AC XY: 1 AN XY: 65302

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000160

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000365 AC: 4 AN: 1094863 Hom.: 0 Cov.: 35 AF XY: 0.00000555 AC XY: 2 AN XY: 360331

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000742

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

Bravo AF: 0.0000189

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

Mar 25, 2024

The c.1570T>A (p.F524I) alteration is located in exon 5 (coding exon 4) of the ZNF630 gene. This alteration results from a T to A substitution at nucleotide position 1570, causing the phenylalanine (F) at amino acid position 524 to be replaced by an isoleucine (I). 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	Pathogenic	0.93
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	.;T;T;.
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.43	T;T;.;T
M_CAP	Benign	0.0066	T
MetaRNN	Uncertain	0.56	D;D;D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Pathogenic	3.4	.;M;M;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.8	.;.;D;D
REVEL	Benign	0.18
Sift	Pathogenic	0.0	.;.;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.99	.;D;D;.
Vest4		0.59
MVP		0.39
MPC		0.24
ClinPred		0.94	D
GERP RS		2.3
Varity_R		0.72
gMVP		0.074

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

LitVar

Other links and lift over

dbSNP: rs1236498771; hg19: chrX-47918261;