Variant X-152920368-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001395254.1(ZNF185):c.571C>T(p.Arg191Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000976 in 1,209,334 control chromosomes in the GnomAD database, including 1 homozygotes. There are 37 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 0.000071 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.00010 ( 1 hom. 36 hem. )

Consequence

ZNF185
NM_001395254.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.295

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07052457).

BS2

High Hemizygotes in GnomAdExome4 at 36 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF185	NM_001395254.1 linkuse as main transcript	c.571C>T	p.Arg191Trp	missense_variant	9/25	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.571C>T	p.Arg191Trp	missense_variant	9/25		NM_001395254.1	ENSP00000512166.1		A0A8Q3WKR1

Frequencies

GnomAD3 genomes

AF:

0.0000714

AC:

AN:

112028

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34186

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000188

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:

0.000113

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000177

AC:

AN:

180531

Hom.:

AF XY:

0.000150

AC XY:

AN XY:

66811

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000696

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000527

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000112

Gnomad OTH exome

AF:

0.000676

GnomAD4 exome

AF:

0.000100

AC:

110

AN:

1097306

Hom.:

Cov.:

AF XY:

0.0000992

AC XY:

AN XY:

363034

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000682

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000962

Gnomad4 OTH exome

AF:

0.0000869

GnomAD4 genome

AF:

0.0000714

AC:

AN:

112028

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34186

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000188

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000113

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000102

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000305

AC:

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.571C>T (p.R191W) alteration is located in exon 8 (coding exon 8) of the ZNF185 gene. This alteration results from a C to T substitution at nucleotide position 571, causing the arginine (R) at amino acid position 191 to be replaced by a tryptophan (W). 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

0.21

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.096

.;.;.;.;T;.;.

FATHMM_MKL

Benign

0.19

LIST_S2

Uncertain

0.91

D;D;D;D;D;.;D

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.071

T;T;T;T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.8

L;L;L;L;L;L;.

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-5.2

D;D;D;D;D;.;D

REVEL

Benign

0.27

Sift

Pathogenic

0.0

D;D;D;D;D;.;D

Sift4G

Uncertain

0.0070

D;D;D;D;D;D;D

Polyphen

0.99, 0.98

.;D;.;.;D;.;.

Vest4

0.46

MVP

0.061

MPC

0.32

ClinPred

0.18

GERP RS

1.4

Varity_R

0.29

gMVP

0.26

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