Variant 19-12390629-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001080821.3(ZNF799):c.1769G>A(p.Cys590Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000239 in 1,461,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

ZNF799
NM_001080821.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.944

Variant links:

Genes affected

ZNF799 (HGNC:28071): (zinc finger protein 799) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription 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]

ZNF799 links:

ZNF799 (HGNC:):

ZNF799 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.915

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF799	NM_001080821.3 linkuse as main transcript	c.1769G>A	p.Cys590Tyr	missense_variant	4/4	ENST00000430385.3	NP_001074290.1	Q96GE5-1
ZNF799	NM_001322497.2 linkuse as main transcript	c.1673G>A	p.Cys558Tyr	missense_variant	4/4		NP_001309426.1	D3YTF2
ZNF799	NM_001322498.2 linkuse as main transcript	c.1673G>A	p.Cys558Tyr	missense_variant	5/5		NP_001309427.1	D3YTF2
ZNF799	XM_047439649.1 linkuse as main transcript	c.1769G>A	p.Cys590Tyr	missense_variant	4/4		XP_047295605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF799	ENST00000430385.3 linkuse as main transcript	c.1769G>A	p.Cys590Tyr	missense_variant	4/4	2	NM_001080821.3	ENSP00000411084.2	Q96GE5-1
ZNF799	ENST00000460935.1 linkuse as main transcript	n.3463G>A		non_coding_transcript_exon_variant	3/3	1
ZNF799	ENST00000419318.5 linkuse as main transcript	c.1673G>A	p.Cys558Tyr	missense_variant	4/4	2		ENSP00000415278.1	D3YTF2
ENSG00000268744	ENST00000435033.1 linkuse as main transcript	n.208-6942G>A		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250570

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135672

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:

0.00

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1461620

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727098

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:

0.0000288

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.00000378

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

Sep 29, 2023

The c.1769G>A (p.C590Y) alteration is located in exon 4 (coding exon 4) of the ZNF799 gene. This alteration results from a G to A substitution at nucleotide position 1769, causing the cysteine (C) at amino acid position 590 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

Uncertain

0.50

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.17

.;T

Eigen

Benign

-0.044

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.32

T;T

M_CAP

Benign

0.0055

MetaRNN

Pathogenic

0.91

D;D

MetaSVM

Uncertain

-0.022

MutationAssessor

Pathogenic

3.9

.;H

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-8.7

D;D

REVEL

Benign

0.21

Sift

Uncertain

0.025

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.25

MutPred

0.93

.;Gain of phosphorylation at C590 (P = 0.0454);

MVP

0.87

MPC

0.61

ClinPred

0.73

GERP RS

0.19

Varity_R

0.45

gMVP

0.15

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