Variant X-152914826-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001395254.1(ZNF185):c.151C>T(p.Arg51Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00026 in 1,181,222 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 96 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 0.00031 ( 0 hom., 12 hem., cov: 22)

Exomes 𝑓: 0.00026 ( 0 hom. 84 hem. )

Consequence

ZNF185
NM_001395254.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0980

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013646632).

BS2

High Hemizygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF185	NM_001395254.1 linkuse as main transcript	c.151C>T	p.Arg51Cys	missense_variant	3/25	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.151C>T	p.Arg51Cys	missense_variant	3/25		NM_001395254.1	ENSP00000512166.1		A0A8Q3WKR1

Frequencies

GnomAD3 genomes

AF:

0.000316

AC:

AN:

110691

Hom.:

Cov.:

AF XY:

0.000365

AC XY:

AN XY:

32911

show subpopulations

Gnomad AFR

AF:

0.0000988

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:

0.000672

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000530

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000204

AC:

AN:

132236

Hom.:

AF XY:

0.000170

AC XY:

AN XY:

41070

show subpopulations

Gnomad AFR exome

AF:

0.000235

Gnomad AMR exome

AF:

0.0000461

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000985

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000159

Gnomad NFE exome

AF:

0.000385

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000255

AC:

273

AN:

1070483

Hom.:

Cov.:

AF XY:

0.000241

AC XY:

AN XY:

348173

show subpopulations

Gnomad4 AFR exome

AF:

0.0000773

Gnomad4 AMR exome

AF:

0.000196

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000555

Gnomad4 NFE exome

AF:

0.000285

Gnomad4 OTH exome

AF:

0.000177

GnomAD4 genome

AF:

0.000307

AC:

AN:

110739

Hom.:

Cov.:

AF XY:

0.000364

AC XY:

AN XY:

32971

show subpopulations

Gnomad4 AFR

AF:

0.0000657

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000672

Gnomad4 NFE

AF:

0.000530

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000625

Hom.:

Bravo

AF:

0.000238

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000607

AC:

ExAC

AF:

0.000363

AC:

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

Apr 08, 2022

The c.151C>T (p.R51C) alteration is located in exon 2 (coding exon 2) of the ZNF185 gene. This alteration results from a C to T substitution at nucleotide position 151, causing the arginine (R) at amino acid position 51 to be replaced by a cysteine (C). 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

0.093

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.053

.;.;.;.;T;.

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.77

T;T;T;T;T;.

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.014

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L;L;L;L;L

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-3.2

D;D;D;D;D;D

REVEL

Benign

0.031

Sift

Benign

0.13

T;T;T;T;T;D

Sift4G

Benign

0.099

T;T;T;T;T;T

Polyphen

0.0080

.;B;.;.;B;.

Vest4

0.14

MVP

0.030

MPC

0.068

ClinPred

0.020

GERP RS

2.2

Varity_R

0.11

gMVP

0.15

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