X-47976318-C-T

Variant names:

• chrX-47976318-C-T
• NM_001007088.2:c.1712G>A

Variant summary

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

The NM_001007088.2(ZNF182):​c.1712G>A​(p.Arg571Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000915 in 1,093,181 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: ZNF182 NM_001007088.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0800

Genes affected

ZNF182 (HGNC:13001): (zinc finger protein 182) Zinc-finger proteins bind nucleic acids and play important roles in various cellular functions, including cell proliferation, differentiation, and apoptosis. This gene encodes a zinc finger protein, and belongs to the krueppel C2H2-type zinc-finger protein family. It may be involved in transcriptional regulation. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, May 2010]

ZNF81 (HGNC:13156): (zinc finger protein 81) This gene encodes a protein that likely functions as a transcription factor. The protein contains an N-terminal KRAB domain and several C2H2-type zinc finger motifs. Mutations in this gene cause an X-linked form of intellectual disability (MRX45). Microduplication of a region of chromosome X including this gene has also been associated with other forms of intellectual disability. [provided by RefSeq, Jul 2017]

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=0.20452917).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF182	NM_001007088.2	c.1712G>A	p.Arg571Lys	missense_variant	Exon 6 of 6	ENST00000376943.8	NP_001007089.1
ZNF182	NM_001178099.2	c.1769G>A	p.Arg590Lys	missense_variant	Exon 7 of 7		NP_001171570.1
ZNF182	NM_006962.2	c.1769G>A	p.Arg590Lys	missense_variant	Exon 7 of 7		NP_008893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF182	ENST00000376943.8	c.1712G>A	p.Arg571Lys	missense_variant	Exon 6 of 6	1	NM_001007088.2	ENSP00000366142.4
ZNF182	ENST00000396965.5	c.1769G>A	p.Arg590Lys	missense_variant	Exon 7 of 7	2		ENSP00000380165.1
ZNF81	ENST00000376950.4	c.278-26210C>T		intron_variant	Intron 4 of 4	5		ENSP00000366149.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.15e-7 AC: 1 AN: 1093181 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 359131

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000218

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1769G>A (p.R590K) alteration is located in exon 7 (coding exon 4) of the ZNF182 gene. This alteration results from a G to A substitution at nucleotide position 1769, causing the arginine (R) at amino acid position 590 to be replaced by a lysine (K). 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	0.35
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	.;T
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.23	T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	.;L
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.19
Sift	Benign	0.050	D;T
Sift4G	Benign	0.12	T;T
Polyphen		0.91	.;P
Vest4		0.18
MutPred		0.64		.;Gain of methylation at R590 (P = 0.016);
MVP		0.34
MPC		1.3
ClinPred		0.77	D
GERP RS		4.9
Varity_R		0.48
gMVP		0.31

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-47835717;