Variant X-152917145-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001395254.1(ZNF185):c.239G>C(p.Arg80Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000024 in 1,209,886 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000025 ( 0 hom. 12 hem. )

Consequence

ZNF185
NM_001395254.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.29114112).

BS2

High Hemizygotes in GnomAdExome4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF185	NM_001395254.1 linkuse as main transcript	c.239G>C	p.Arg80Thr	missense_variant	5/25	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.239G>C	p.Arg80Thr	missense_variant	5/25		NM_001395254.1	ENSP00000512166.1		A0A8Q3WKR1

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112278

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34444

show subpopulations

Gnomad AFR

AF:

0.0000647

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000551

AC:

AN:

181342

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67494

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1097608

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

363302

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000321

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112278

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34444

show subpopulations

Gnomad4 AFR

AF:

0.0000647

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

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

Jan 04, 2024

The c.239G>C (p.R80T) alteration is located in exon 4 (coding exon 4) of the ZNF185 gene. This alteration results from a G to C substitution at nucleotide position 239, causing the arginine (R) at amino acid position 80 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

0.21

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.011

.;.;.;.;T;.

FATHMM_MKL

Benign

0.23

LIST_S2

Uncertain

0.89

D;D;D;D;D;.

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.29

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.8

L;L;L;L;L;L

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.0

D;D;D;D;D;.

REVEL

Benign

0.073

Sift

Uncertain

0.0040

D;D;D;D;D;.

Sift4G

Benign

0.36

T;T;T;T;T;T

Polyphen

0.95, 0.21

.;P;.;.;B;.

Vest4

0.40

MVP

0.085

MPC

0.38

ClinPred

0.68

GERP RS

3.2

Varity_R

0.22

gMVP

0.19

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