Variant X-152914832-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001395254.1(ZNF185):c.157A>G(p.Ile53Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.4e-7 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

ZNF185
NM_001395254.1 missense, splice_region

Scores

Splicing: ADA: 0.2998

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.224

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03941253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF185	NM_001395254.1 linkuse as main transcript	c.157A>G	p.Ile53Val	missense_variant, splice_region_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.157A>G	p.Ile53Val	missense_variant, splice_region_variant	3/25		NM_001395254.1	ENSP00000512166	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000765

AC:

AN:

130802

Hom.:

AF XY:

0.00

AC XY:

AN XY:

40314

show subpopulations

Gnomad AFR exome

AF:

0.000119

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

9.35e-7

AC:

AN:

1069111

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

347569

show subpopulations

Gnomad4 AFR exome

AF:

0.0000387

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 20, 2024

The c.157A>G (p.I53V) alteration is located in exon 2 (coding exon 2) of the ZNF185 gene. This alteration results from a A to G substitution at nucleotide position 157, causing the isoleucine (I) at amino acid position 53 to be replaced by a valine (V). 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

0.077

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.94

CADD

Benign

9.5

DANN

Benign

0.70

DEOGEN2

Benign

0.0018

.;.;.;.;T;.

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.65

T;T;T;T;T;.

M_CAP

Benign

0.013

MetaRNN

Benign

0.039

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;L;L;L;L

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.30

N;N;N;N;N;.

REVEL

Benign

0.019

Sift

Benign

0.29

T;T;T;T;T;.

Sift4G

Benign

0.41

T;T;T;T;T;T

Polyphen

0.023, 0.11

.;B;.;.;B;.

Vest4

0.10

MutPred

0.15

Gain of MoRF binding (P = 0.2097);Gain of MoRF binding (P = 0.2097);Gain of MoRF binding (P = 0.2097);Gain of MoRF binding (P = 0.2097);Gain of MoRF binding (P = 0.2097);Gain of MoRF binding (P = 0.2097);

MVP

0.014

MPC

0.053

ClinPred

0.014

GERP RS

1.6

Varity_R

0.036

gMVP

0.097

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.30

dbscSNV1_RF

Benign

0.57

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.20

Position offset: 6

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