X-47976864-C-T

Variant summary

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

The NM_001007088.2(ZNF182):​c.1166G>A​(p.Gly389Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,094,945 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.000014 ( 0 hom. 6 hem. )

Consequence

ZNF182
NM_001007088.2 missense

Scores

2
4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.55
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High Hemizygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF182NM_001007088.2 linkc.1166G>A p.Gly389Glu missense_variant Exon 6 of 6 ENST00000376943.8 NP_001007089.1 P17025-2
ZNF182NM_001178099.2 linkc.1223G>A p.Gly408Glu missense_variant Exon 7 of 7 NP_001171570.1 P17025-1
ZNF182NM_006962.2 linkc.1223G>A p.Gly408Glu 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.1166G>A p.Gly389Glu missense_variant Exon 6 of 6 1 NM_001007088.2 ENSP00000366142.4 P17025-2
ZNF182ENST00000396965.5 linkc.1223G>A p.Gly408Glu missense_variant Exon 7 of 7 2 ENSP00000380165.1 P17025-1
ZNF81ENST00000376950.4 linkc.278-25664C>T intron_variant Intron 4 of 4 5 ENSP00000366149.4 B1AJV2

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD3 exomes
AF:
0.0000113
AC:
2
AN:
177608
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
62612
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000375
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000125
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
15
AN:
1094945
Hom.:
0
Cov.:
31
AF XY:
0.0000166
AC XY:
6
AN XY:
360601
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000575
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:
0.0000155
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1223G>A (p.G408E) 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 1223, causing the glycine (G) at amino acid position 408 to be replaced by a glutamic acid (E). 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
0.57
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.39
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.098
.;T
FATHMM_MKL
Benign
0.018
N
LIST_S2
Benign
0.68
T;T
M_CAP
Benign
0.053
D
MetaRNN
Uncertain
0.46
T;T
MetaSVM
Benign
-0.69
T
MutationAssessor
Benign
1.9
.;L
PrimateAI
Uncertain
0.75
T
PROVEAN
Pathogenic
-5.1
D;D
REVEL
Benign
0.20
Sift
Benign
0.086
T;T
Sift4G
Uncertain
0.016
D;D
Polyphen
1.0
.;D
Vest4
0.56
MutPred
0.54
.;Gain of relative solvent accessibility (P = 0.1259);
MVP
0.39
MPC
1.4
ClinPred
0.93
D
GERP RS
4.3
Varity_R
0.72
gMVP
0.20

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: rs781830259; hg19: chrX-47836263; API