X-47983299-T-C

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001007088.2(ZNF182):c.128A>G(p.Asn43Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 1,209,588 control chromosomes in the GnomAD database, including 1 homozygotes. There are 89 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., 6 hem., cov: 22)

Exomes 𝑓: 0.00025 ( 1 hom. 83 hem. )

Consequence

ZNF182
NM_001007088.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0710

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]

ZNF182 links:

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]

ZNF81 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.087296635).

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF182	NM_001007088.2 link	c.128A>G	p.Asn43Ser	missense_variant	Exon 4 of 6	ENST00000376943.8	NP_001007089.1	P17025-2
ZNF182	NM_001178099.2 link	c.185A>G	p.Asn62Ser	missense_variant	Exon 5 of 7		NP_001171570.1	P17025-1
ZNF182	NM_006962.2 link	c.185A>G	p.Asn62Ser	missense_variant	Exon 5 of 7		NP_008893.1	P17025-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF182	ENST00000376943.8 link	c.128A>G	p.Asn43Ser	missense_variant	Exon 4 of 6	1	NM_001007088.2	ENSP00000366142.4	P17025-2
ZNF182	ENST00000396965.5 link	c.185A>G	p.Asn62Ser	missense_variant	Exon 5 of 7	2		ENSP00000380165.1	P17025-1
ZNF81	ENST00000376950.4 link	c.278-19229T>C		intron_variant	Intron 4 of 4	5		ENSP00000366149.4	B1AJV2
ZNF630	ENST00000428463.5 link	n.*783A>G		downstream_gene_variant		2		ENSP00000400030.1	F8WCH7

Frequencies

GnomAD3 genomes

AF:

0.000170

AC:

AN:

111632

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

33804

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000358

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000115

AC:

AN:

182848

Hom.:

AF XY:

0.000148

AC XY:

AN XY:

67418

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000268

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000209

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000246

AC:

270

AN:

1097956

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

363366

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.000303

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.000170

AC:

AN:

111632

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

33804

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.000358

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000388

Hom.:

Bravo

AF:

0.000144

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000595

AC:

ExAC

AF:

0.000165

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.185A>G (p.N62S) alteration is located in exon 5 (coding exon 2) of the ZNF182 gene. This alteration results from a A to G substitution at nucleotide position 185, causing the asparagine (N) at amino acid position 62 to be replaced by a serine (S). 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

0.26

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

.;T

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.0099

MetaRNN

Benign

0.087

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

.;M

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.5

N;N

REVEL

Benign

0.082

Sift

Benign

0.13

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.018

.;B

Vest4

0.18

MVP

0.37

MPC

0.43

ClinPred

0.023

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.061

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over