Variant X-152915163-G-A 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.184G>A(p.Ala62Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,208,790 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 44 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 0.000027 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.00011 ( 0 hom. 43 hem. )

Consequence

ZNF185
NM_001395254.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.834

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=0.103814125).

BS2

High Hemizygotes in GnomAdExome4 at 43 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF185	NM_001395254.1 link	c.184G>A	p.Ala62Thr	missense_variant	4/25	ENST00000695776.1	NP_001382183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF185	ENST00000695776.1 link	c.184G>A	p.Ala62Thr	missense_variant	4/25		NM_001395254.1	ENSP00000512166.1		A0A8Q3WKR1

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

112022

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

34228

show subpopulations

Gnomad AFR

AF:

0.0000324

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:

0.0000377

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000675

AC:

AN:

177759

Hom.:

AF XY:

0.0000618

AC XY:

AN XY:

64719

show subpopulations

Gnomad AFR exome

AF:

0.0000814

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000108

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000101

Gnomad OTH exome

AF:

0.000229

GnomAD4 exome

AF:

0.000111

AC:

122

AN:

1096768

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

362564

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000557

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000137

Gnomad4 OTH exome

AF:

0.0000652

GnomAD4 genome

AF:

0.0000268

AC:

AN:

112022

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

34228

show subpopulations

Gnomad4 AFR

AF:

0.0000324

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:

0.0000377

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000491

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000578

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

Feb 01, 2023

The c.184G>A (p.A62T) alteration is located in exon 3 (coding exon 3) of the ZNF185 gene. This alteration results from a G to A substitution at nucleotide position 184, causing the alanine (A) at amino acid position 62 to be replaced by a threonine (T). 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

0.092

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.026

.;.;.;.;T;.

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.71

T;T;T;T;T;.

M_CAP

Benign

0.035

MetaRNN

Benign

0.10

T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.8

L;L;L;L;L;L

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.9

N;N;N;N;N;.

REVEL

Benign

0.074

Sift

Uncertain

0.027

D;D;D;D;D;.

Sift4G

Benign

0.42

T;T;T;T;T;T

Polyphen

1.0, 1.0

.;D;.;.;D;.

Vest4

0.25

MVP

0.17

MPC

0.065

ClinPred

0.043

GERP RS

2.2

Varity_R

0.062

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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