X-47977557-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001007088.2(ZNF182):​c.473G>A​(p.Ser158Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000366 in 1,093,758 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000037 ( 0 hom. 1 hem. )

Consequence

ZNF182
NM_001007088.2 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.172
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.052458376).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF182NM_001007088.2 linkc.473G>A p.Ser158Asn missense_variant Exon 6 of 6 ENST00000376943.8 NP_001007089.1 P17025-2
ZNF182NM_001178099.2 linkc.530G>A p.Ser177Asn missense_variant Exon 7 of 7 NP_001171570.1 P17025-1
ZNF182NM_006962.2 linkc.530G>A p.Ser177Asn missense_variant Exon 7 of 7 NP_008893.1 P17025-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF182ENST00000376943.8 linkc.473G>A p.Ser158Asn missense_variant Exon 6 of 6 1 NM_001007088.2 ENSP00000366142.4 P17025-2
ZNF182ENST00000396965.5 linkc.530G>A p.Ser177Asn missense_variant Exon 7 of 7 2 ENSP00000380165.1 P17025-1
ZNF81ENST00000376950.4 linkc.278-24971C>T intron_variant Intron 4 of 4 5 ENSP00000366149.4 B1AJV2

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD3 exomes
AF:
0.0000170
AC:
3
AN:
176520
Hom.:
0
AF XY:
0.0000162
AC XY:
1
AN XY:
61772
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000220
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000366
AC:
4
AN:
1093758
Hom.:
0
Cov.:
30
AF XY:
0.00000278
AC XY:
1
AN XY:
359766
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000133
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 28, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.530G>A (p.S177N) 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 530, causing the serine (S) at amino acid position 177 to be replaced by an asparagine (N). 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
0.073
BayesDel_addAF
Benign
-0.82
T
BayesDel_noAF
Benign
-1.1
CADD
Benign
1.7
DANN
Benign
0.81
DEOGEN2
Benign
0.0079
.;T
FATHMM_MKL
Benign
0.00053
N
LIST_S2
Benign
0.023
T;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.052
T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.54
.;N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
0.24
N;N
REVEL
Benign
0.030
Sift
Benign
0.63
T;T
Sift4G
Benign
0.50
T;T
Polyphen
0.0010
.;B
Vest4
0.13
MutPred
0.41
.;Loss of phosphorylation at S177 (P = 0.0959);
MVP
0.24
MPC
0.38
ClinPred
0.013
T
GERP RS
1.5
Varity_R
0.056
gMVP
0.19

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs782325713; hg19: chrX-47836956; API