X-47977683-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001007088.2(ZNF182):​c.347G>A​(p.Arg116His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000215 in 1,209,210 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 3 hem., cov: 23)
Exomes 𝑓: 0.000013 ( 0 hom. 1 hem. )

Consequence

ZNF182
NM_001007088.2 missense

Scores

17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.210
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 Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.030558348).
BP6
Variant X-47977683-C-T is Benign according to our data. Variant chrX-47977683-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2508299.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF182NM_001007088.2 linkc.347G>A p.Arg116His missense_variant Exon 6 of 6 ENST00000376943.8 NP_001007089.1 P17025-2
ZNF182NM_001178099.2 linkc.404G>A p.Arg135His missense_variant Exon 7 of 7 NP_001171570.1 P17025-1
ZNF182NM_006962.2 linkc.404G>A p.Arg135His 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.347G>A p.Arg116His missense_variant Exon 6 of 6 1 NM_001007088.2 ENSP00000366142.4 P17025-2
ZNF182ENST00000396965.5 linkc.404G>A p.Arg135His missense_variant Exon 7 of 7 2 ENSP00000380165.1 P17025-1
ZNF81ENST00000376950.4 linkc.278-24845C>T intron_variant Intron 4 of 4 5 ENSP00000366149.4 B1AJV2

Frequencies

GnomAD3 genomes
AF:
0.000107
AC:
12
AN:
112225
Hom.:
0
Cov.:
23
AF XY:
0.0000872
AC XY:
3
AN XY:
34389
show subpopulations
Gnomad AFR
AF:
0.000356
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000440
AC:
8
AN:
181767
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
66421
show subpopulations
Gnomad AFR exome
AF:
0.000533
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000724
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:
0.0000128
AC:
14
AN:
1096985
Hom.:
0
Cov.:
30
AF XY:
0.00000276
AC XY:
1
AN XY:
362413
show subpopulations
Gnomad4 AFR exome
AF:
0.000379
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000331
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000238
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
AF:
0.000107
AC:
12
AN:
112225
Hom.:
0
Cov.:
23
AF XY:
0.0000872
AC XY:
3
AN XY:
34389
show subpopulations
Gnomad4 AFR
AF:
0.000356
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000188
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000356
Hom.:
1
Bravo
AF:
0.000128
ESP6500AA
AF:
0.000522
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
May 26, 2023
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.084
BayesDel_addAF
Benign
-0.84
T
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.010
DANN
Benign
0.71
DEOGEN2
Benign
0.0049
.;T
FATHMM_MKL
Benign
0.000030
N
LIST_S2
Benign
0.033
T;T
M_CAP
Benign
0.0018
T
MetaRNN
Benign
0.031
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
-0.81
.;N
PrimateAI
Benign
0.18
T
PROVEAN
Benign
2.3
N;N
REVEL
Benign
0.013
Sift
Benign
0.62
T;T
Sift4G
Benign
0.55
T;T
Polyphen
0.0
.;B
Vest4
0.051
MVP
0.16
MPC
0.51
ClinPred
0.015
T
GERP RS
-4.9
Varity_R
0.026
gMVP
0.056

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: rs140603964; hg19: chrX-47837082; COSMIC: COSV59359735; API