Variant X-152922743-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001395254.1(ZNF185):c.764C>T(p.Ala255Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000584 in 1,199,257 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 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 0.000027 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000062 ( 0 hom. 19 hem. )

Consequence

ZNF185
NM_001395254.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0380

Variant links:

Genes affected

ZNF185 (HGNC:12976): (zinc finger protein 185 with LIM domain) Zinc-finger proteins bind nucleic acids and play important roles in various cellular functions, including cell proliferation, differentiation, and apoptosis. This gene encodes a LIM-domain zinc finger protein. The LIM domain is composed of two contiguous zinc finger domains, separated by a two-amino acid residue hydrophobic linker. The LIM domain mediates protein:protein interactions. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, May 2010]

ZNF185 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029227883).

BP6

Variant X-152922743-C-T is Benign according to our data. Variant chrX-152922743-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2469439.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF185	NM_001395254.1 linkuse as main transcript	c.764C>T	p.Ala255Val	missense_variant	12/25	ENST00000695776.1	NP_001382183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF185	ENST00000695776.1 linkuse as main transcript	c.764C>T	p.Ala255Val	missense_variant	12/25		NM_001395254.1	ENSP00000512166	A2

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112370

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34512

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:

0.0000564

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000768

AC:

AN:

156339

Hom.:

AF XY:

0.0000609

AC XY:

AN XY:

49297

show subpopulations

Gnomad AFR exome

AF:

0.0000956

Gnomad AMR exome

AF:

0.000119

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:

0.000118

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000616

AC:

AN:

1086887

Hom.:

Cov.:

AF XY:

0.0000535

AC XY:

AN XY:

355343

show subpopulations

Gnomad4 AFR exome

AF:

0.0000763

Gnomad4 AMR exome

AF:

0.0000887

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000252

Gnomad4 NFE exome

AF:

0.0000717

Gnomad4 OTH exome

AF:

0.0000219

GnomAD4 genome

AF:

0.0000267

AC:

AN:

112370

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34512

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:

0.0000564

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000582

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 02, 2023

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

-0.60

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.053

DANN

Benign

0.24

DEOGEN2

Benign

0.00035

.;.;.;T;.

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.55

T;T;T;T;.

M_CAP

Benign

0.0018

MetaRNN

Benign

0.029

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.83

.;N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

0.15

N;N;N;N;.

REVEL

Benign

0.029

Sift

Benign

0.55

T;T;T;T;.

Sift4G

Benign

0.89

T;T;T;T;T

Polyphen

0.0010

B;.;.;B;.

Vest4

0.027

MVP

0.14

MPC

0.052

ClinPred

0.0015

GERP RS

-0.68

Varity_R

0.025

gMVP

0.050

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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