Variant 19-44386936-A-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_152354.6(ZNF285):c.1309T>A(p.Phe437Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000404 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

ZNF285
NM_152354.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.34

Variant links:

Genes affected

ZNF285 (HGNC:13079): (zinc finger protein 285) 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. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF285 links:

ENSG00000267173 (HGNC:):

ENSG00000267173 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
ZNF285	NM_152354.6 linkuse as main transcript	c.1309T>A	p.Phe437Ile	missense_variant	4/4	ENST00000614994.5	NP_689567.4	Q96NJ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF285	ENST00000614994.5 linkuse as main transcript	c.1309T>A	p.Phe437Ile	missense_variant	4/4	1	NM_152354.6	ENSP00000483662.1	Q96NJ3-1
ENSG00000267173	ENST00000588212.1 linkuse as main transcript	c.15+10263T>A		intron_variant		2		ENSP00000468271.1	K7ERI5
ZNF285	ENST00000591679.5 linkuse as main transcript	c.1330T>A	p.Phe444Ile	missense_variant	5/5	4		ENSP00000464788.1	K7EIK6
ZNF285	ENST00000544719.6 linkuse as main transcript	c.1309T>A	p.Phe437Ile	missense_variant	4/4	5		ENSP00000439431.2	Q96NJ3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251328

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135824

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:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000404

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

727218

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:

0.0000450

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000227

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

Jun 30, 2024

The c.1309T>A (p.F437I) alteration is located in exon 4 (coding exon 3) of the ZNF285 gene. This alteration results from a T to A substitution at nucleotide position 1309, causing the phenylalanine (F) at amino acid position 437 to be replaced by an isoleucine (I). 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

0.94

BayesDel_addAF

Benign

0.0062

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.78

.;.;T

M_CAP

Benign

0.041

MetaRNN

Uncertain

0.72

D;D;D

MetaSVM

Benign

-0.53

REVEL

Uncertain

0.43

Sift4G

Pathogenic

0.0

D;D;D

Vest4

0.50

MutPred

0.73

Loss of ubiquitination at K435 (P = 0.1264);Loss of ubiquitination at K435 (P = 0.1264);.;

MVP

0.60

ClinPred

0.97

GERP RS

3.4

gMVP

0.028

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