X-47976226-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001007088.2(ZNF182):c.1804G>T(p.Ala602Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000892 in 112,121 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000037 ( 0 hom. 2 hem. )

Failed GnomAD Quality Control

Consequence

ZNF182
NM_001007088.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.101

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.08613497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF182	NM_001007088.2 link	c.1804G>T	p.Ala602Ser	missense_variant	Exon 6 of 6	ENST00000376943.8	NP_001007089.1	P17025-2
ZNF182	NM_001178099.2 link	c.1861G>T	p.Ala621Ser	missense_variant	Exon 7 of 7		NP_001171570.1	P17025-1
ZNF182	NM_006962.2 link	c.1861G>T	p.Ala621Ser	missense_variant	Exon 7 of 7		NP_008893.1	P17025-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF182	ENST00000376943.8 link	c.1804G>T	p.Ala602Ser	missense_variant	Exon 6 of 6	1	NM_001007088.2	ENSP00000366142.4	P17025-2
ZNF182	ENST00000396965.5 link	c.1861G>T	p.Ala621Ser	missense_variant	Exon 7 of 7	2		ENSP00000380165.1	P17025-1
ZNF81	ENST00000376950.4 link	c.278-26302C>A		intron_variant	Intron 4 of 4	5		ENSP00000366149.4	B1AJV2

Frequencies

GnomAD3 genomes

AF:

0.00000892

AC:

AN:

112121

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34281

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000943

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000659

AC:

AN:

151855

Hom.:

AF XY:

0.0000208

AC XY:

AN XY:

48047

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000468

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000374

AC:

AN:

1069341

Hom.:

Cov.:

AF XY:

0.00000576

AC XY:

AN XY:

347211

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000679

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:

0.00000241

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000892

AC:

AN:

112121

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34281

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000943

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1861G>T (p.A621S) alteration is located in exon 7 (coding exon 4) of the ZNF182 gene. This alteration results from a G to T substitution at nucleotide position 1861, causing the alanine (A) at amino acid position 621 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

0.078

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.91

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.0030

.;T

FATHMM_MKL

Benign

0.0049

LIST_S2

Benign

0.15

T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.086

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.17

.;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.94

N;N

REVEL

Benign

0.034

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.046

D;T

Polyphen

0.0020

.;B

Vest4

0.12

MutPred

0.46

.;Gain of glycosylation at A621 (P = 0.0113);

MVP

0.15

MPC

0.38

ClinPred

0.075

GERP RS

1.1

Varity_R

0.078

gMVP

0.12

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