Variant 19-12390560-T-C 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_001080821.3(ZNF799):c.1838A>G(p.Lys613Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,611,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

ZNF799
NM_001080821.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.258

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:

Genome browser will be placed here

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=0.03584665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF799	NM_001080821.3 linkuse as main transcript	c.1838A>G	p.Lys613Arg	missense_variant	4/4	ENST00000430385.3	NP_001074290.1	Q96GE5-1
ZNF799	NM_001322497.2 linkuse as main transcript	c.1742A>G	p.Lys581Arg	missense_variant	4/4		NP_001309426.1	D3YTF2
ZNF799	NM_001322498.2 linkuse as main transcript	c.1742A>G	p.Lys581Arg	missense_variant	5/5		NP_001309427.1	D3YTF2
ZNF799	XM_047439649.1 linkuse as main transcript	c.1838A>G	p.Lys613Arg	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.1838A>G	p.Lys613Arg	missense_variant	4/4	2	NM_001080821.3	ENSP00000411084.2	Q96GE5-1
ZNF799	ENST00000460935.1 linkuse as main transcript	n.3532A>G		non_coding_transcript_exon_variant	3/3	1
ZNF799	ENST00000419318.5 linkuse as main transcript	c.1742A>G	p.Lys581Arg	missense_variant	4/4	2		ENSP00000415278.1	D3YTF2
ENSG00000268744	ENST00000435033.1 linkuse as main transcript	n.208-6873A>G		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000665

AC:

AN:

150420

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000490

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000104

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000359

AC:

AN:

251036

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135770

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:

0.0000705

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1461180

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

726874

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:

0.0000405

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000665

AC:

AN:

150420

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73438

show subpopulations

Gnomad4 AFR

AF:

0.0000490

Gnomad4 AMR

AF:

0.0000661

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000104

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000178

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

Feb 14, 2023

The c.1838A>G (p.K613R) alteration is located in exon 4 (coding exon 4) of the ZNF799 gene. This alteration results from a A to G substitution at nucleotide position 1838, causing the lysine (K) at amino acid position 613 to be replaced by an arginine (R). 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

0.088

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.11

DANN

Benign

0.85

DEOGEN2

Benign

0.0019

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0065

LIST_S2

Benign

0.13

T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.036

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.74

.;N

PrimateAI

Benign

0.32

PROVEAN

Benign

1.3

N;N

REVEL

Benign

0.020

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.046

MutPred

0.30

.;Loss of methylation at K613 (P = 0.0132);

MVP

0.28

MPC

0.071

ClinPred

0.030

Varity_R

0.11

gMVP

0.0064

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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