19-12390807-G-C

Position:

chr19-12390807-G-C

Variant summary

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

The NM_001080821.3(ZNF799):c.1591C>G(p.Pro531Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF799
NM_001080821.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31

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 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=0.20891124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF799	NM_001080821.3 linkuse as main transcript	c.1591C>G	p.Pro531Ala	missense_variant	4/4	ENST00000430385.3	NP_001074290.1	Q96GE5-1
ZNF799	NM_001322497.2 linkuse as main transcript	c.1495C>G	p.Pro499Ala	missense_variant	4/4		NP_001309426.1	D3YTF2
ZNF799	NM_001322498.2 linkuse as main transcript	c.1495C>G	p.Pro499Ala	missense_variant	5/5		NP_001309427.1	D3YTF2
ZNF799	XM_047439649.1 linkuse as main transcript	c.1591C>G	p.Pro531Ala	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.1591C>G	p.Pro531Ala	missense_variant	4/4	2	NM_001080821.3	ENSP00000411084.2	Q96GE5-1
ZNF799	ENST00000460935.1 linkuse as main transcript	n.3285C>G		non_coding_transcript_exon_variant	3/3	1
ZNF799	ENST00000419318.5 linkuse as main transcript	c.1495C>G	p.Pro499Ala	missense_variant	4/4	2		ENSP00000415278.1	D3YTF2
ENSG00000268744	ENST00000435033.1 linkuse as main transcript	n.208-7120C>G		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250618

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.84e-7

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

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

Nov 09, 2024

The c.1591C>G (p.P531A) alteration is located in exon 4 (coding exon 4) of the ZNF799 gene. This alteration results from a C to G substitution at nucleotide position 1591, causing the proline (P) at amino acid position 531 to be replaced by an alanine (A). 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

0.66

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.13

.;T

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.16

T;T

M_CAP

Benign

0.0021

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.6

.;M

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-6.9

D;D

REVEL

Benign

0.077

Sift

Uncertain

0.0040

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

0.99

.;D

Vest4

0.16

MutPred

0.45

.;Loss of ubiquitination at K535 (P = 0.0694);

MVP

0.48

MPC

0.47

ClinPred

0.83

GERP RS

0.23

Varity_R

0.18

gMVP

0.0072

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