Genetic Variant ZNF182:p.Gly389Glu (chrX-47976864-C-T) – ACMG Classification: Likely_benign (-4 pts)

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

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]

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:

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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
ZNF182	NM_001007088.2 link	c.1166G>A	p.Gly389Glu	missense_variant	Exon 6 of 6	ENST00000376943.8	NP_001007089.1	P17025-2
ZNF182	NM_001178099.2 link	c.1223G>A	p.Gly408Glu	missense_variant	Exon 7 of 7		NP_001171570.1	P17025-1
ZNF182	NM_006962.2 link	c.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	UniProt
ZNF182	ENST00000376943.8 link	c.1166G>A	p.Gly389Glu	missense_variant	Exon 6 of 6	1	NM_001007088.2	ENSP00000366142.4	P17025-2
ZNF182	ENST00000396965.5 link	c.1223G>A	p.Gly408Glu	missense_variant	Exon 7 of 7	2		ENSP00000380165.1	P17025-1
ZNF81	ENST00000376950.4 link	c.278-25664C>T		intron_variant	Intron 4 of 4	5		ENSP00000366149.4	B1AJV2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000113

AC:

AN:

177608

Hom.:

AF XY:

0.00

AC XY:

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:

AN:

1094945

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

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.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.098

.;T

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.053

MetaRNN

Uncertain

0.46

T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.9

.;L

PrimateAI

Uncertain

0.75

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

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.

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