Variant X-152914721-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001395254.1(ZNF185):c.46C>T(p.Pro16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000092 in 1,087,043 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 21)

Exomes 𝑓: 9.2e-7 ( 0 hom. 0 hem. )

Consequence

ZNF185
NM_001395254.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.184

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08966452).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF185	NM_001395254.1 linkuse as main transcript	c.46C>T	p.Pro16Ser	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.46C>T	p.Pro16Ser	missense_variant	3/25		NM_001395254.1	ENSP00000512166.1		A0A8Q3WKR1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.20e-7

AC:

AN:

1087043

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

355591

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:

0.00000120

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

Apr 03, 2023

The c.46C>T (p.P16S) 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 46, causing the proline (P) at amino acid position 16 to be replaced by a serine (S). 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

0.10

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.064

.;.;.;.;T;.

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.73

T;T;T;T;T;.

M_CAP

Benign

0.023

MetaRNN

Benign

0.090

T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

L;L;L;L;L;L

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.8

D;D;D;D;D;.

REVEL

Benign

0.012

Sift

Benign

0.17

T;T;T;T;T;.

Sift4G

Uncertain

0.054

T;T;T;T;T;T

Polyphen

0.21

.;B;.;.;B;.

Vest4

0.20

MutPred

0.24

Loss of catalytic residue at P16 (P = 0.0018);Loss of catalytic residue at P16 (P = 0.0018);Loss of catalytic residue at P16 (P = 0.0018);Loss of catalytic residue at P16 (P = 0.0018);Loss of catalytic residue at P16 (P = 0.0018);Loss of catalytic residue at P16 (P = 0.0018);

MVP

0.030

MPC

0.064

ClinPred

0.17

GERP RS

3.0

Varity_R

0.093

gMVP

0.54

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over