X-47977586-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001007088.2(ZNF182):c.444G>A(p.Met148Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000706 in 1,204,675 control chromosomes in the GnomAD database, including 1 homozygotes. There are 20 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 1 hom., 9 hem., cov: 23)

Exomes 𝑓: 0.000039 ( 0 hom. 11 hem. )

Consequence

ZNF182
NM_001007088.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0300

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00998497).

BS2

High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF182	NM_001007088.2 link	c.444G>A	p.Met148Ile	missense_variant	Exon 6 of 6	ENST00000376943.8	NP_001007089.1	P17025-2
ZNF182	NM_001178099.2 link	c.501G>A	p.Met167Ile	missense_variant	Exon 7 of 7		NP_001171570.1	P17025-1
ZNF182	NM_006962.2 link	c.501G>A	p.Met167Ile	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.444G>A	p.Met148Ile	missense_variant	Exon 6 of 6	1	NM_001007088.2	ENSP00000366142.4	P17025-2
ZNF182	ENST00000396965.5 link	c.501G>A	p.Met167Ile	missense_variant	Exon 7 of 7	2		ENSP00000380165.1	P17025-1
ZNF81	ENST00000376950.4 link	c.278-24942C>T		intron_variant	Intron 4 of 4	5		ENSP00000366149.4	B1AJV2

Frequencies

GnomAD3 genomes

AF:

0.000374

AC:

AN:

112188

Hom.:

Cov.:

AF XY:

0.000262

AC XY:

AN XY:

34384

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000941

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:

0.00132

GnomAD3 exomes

AF:

0.000130

AC:

AN:

176856

Hom.:

AF XY:

0.0000806

AC XY:

AN XY:

62028

show subpopulations

Gnomad AFR exome

AF:

0.00161

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000118

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000394

AC:

AN:

1092438

Hom.:

Cov.:

AF XY:

0.0000307

AC XY:

AN XY:

358396

show subpopulations

Gnomad4 AFR exome

AF:

0.00130

Gnomad4 AMR exome

AF:

0.0000580

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000755

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000654

GnomAD4 genome

AF:

0.000374

AC:

AN:

112237

Hom.:

Cov.:

AF XY:

0.000261

AC XY:

AN XY:

34443

show subpopulations

Gnomad4 AFR

AF:

0.00126

Gnomad4 AMR

AF:

0.0000940

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:

0.00131

Alfa

AF:

0.0000762

Hom.:

Bravo

AF:

0.000461

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000157

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.501G>A (p.M167I) 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 501, causing the methionine (M) at amino acid position 167 to be replaced by an isoleucine (I). 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

0.13

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0052

.;T

FATHMM_MKL

Benign

0.00073

LIST_S2

Benign

0.0084

T;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.81

.;L

PrimateAI

Benign

0.29

PROVEAN

Benign

0.070

N;N

REVEL

Benign

0.044

Sift

Benign

0.035

D;D

Sift4G

Benign

0.20

T;T

Polyphen

0.0

.;B

Vest4

0.088

MutPred

0.75

.;Loss of disorder (P = 0.0817);

MVP

0.19

MPC

0.46

ClinPred

0.0087

GERP RS

2.8

Varity_R

0.18

gMVP

0.13

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