Variant 19-43914099-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003425.4(ZNF45):c.1337G>A(p.Cys446Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ZNF45
NM_003425.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.56

Variant links:

Genes affected

ZNF45 (HGNC:13111): (zinc finger protein 45) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF45 links:

ZNF45-AS1 (HGNC:):

ZNF45-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF45	NM_003425.4 linkuse as main transcript	c.1337G>A	p.Cys446Tyr	missense_variant	10/10	ENST00000269973.10	NP_003416.1	Q02386

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF45	ENST00000269973.10 linkuse as main transcript	c.1337G>A	p.Cys446Tyr	missense_variant	10/10	2	NM_003425.4	ENSP00000269973.4		Q02386

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251210

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Dec 09, 2023

The c.1337G>A (p.C446Y) alteration is located in exon 10 (coding exon 4) of the ZNF45 gene. This alteration results from a G to A substitution at nucleotide position 1337, causing the cysteine (C) at amino acid position 446 to be replaced by a tyrosine (Y). 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

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.076

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

T;T;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.28

.;T;.

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.71

D;D;D

MetaSVM

Uncertain

0.64

MutationAssessor

Pathogenic

3.5

H;H;H

MutationTaster

Benign

0.94

D;D

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-11

D;.;.

REVEL

Uncertain

0.51

Sift

Pathogenic

0.0

D;.;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.51

MutPred

0.69

Gain of ubiquitination at K445 (P = 0.0719);Gain of ubiquitination at K445 (P = 0.0719);Gain of ubiquitination at K445 (P = 0.0719);

MVP

0.94

MPC

0.97

ClinPred

1.0

GERP RS

3.6

Varity_R

0.90

gMVP

0.37

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