Variant 19-12390941-C-G 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.1457G>C(p.Ser486Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000014 ( 0 hom. )

Consequence

ZNF799
NM_001080821.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -8.22

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 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=0.04332781).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF799	NM_001080821.3 linkuse as main transcript	c.1457G>C	p.Ser486Thr	missense_variant	4/4	ENST00000430385.3	NP_001074290.1	Q96GE5-1
ZNF799	NM_001322497.2 linkuse as main transcript	c.1361G>C	p.Ser454Thr	missense_variant	4/4		NP_001309426.1	D3YTF2
ZNF799	NM_001322498.2 linkuse as main transcript	c.1361G>C	p.Ser454Thr	missense_variant	5/5		NP_001309427.1	D3YTF2
ZNF799	XM_047439649.1 linkuse as main transcript	c.1457G>C	p.Ser486Thr	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.1457G>C	p.Ser486Thr	missense_variant	4/4	2	NM_001080821.3	ENSP00000411084.2	Q96GE5-1
ZNF799	ENST00000460935.1 linkuse as main transcript	n.3151G>C		non_coding_transcript_exon_variant	3/3	1
ZNF799	ENST00000419318.5 linkuse as main transcript	c.1361G>C	p.Ser454Thr	missense_variant	4/4	2		ENSP00000415278.1	D3YTF2
ENSG00000268744	ENST00000435033.1 linkuse as main transcript	n.208-7254G>C		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251048

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135778

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461760

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727174

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 07, 2024

The c.1457G>C (p.S486T) alteration is located in exon 4 (coding exon 4) of the ZNF799 gene. This alteration results from a G to C substitution at nucleotide position 1457, causing the serine (S) at amino acid position 486 to be replaced by a threonine (T). 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

0.15

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.15

DANN

Benign

0.34

DEOGEN2

Benign

0.0052

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.093

T;T

M_CAP

Benign

0.00084

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.38

.;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.67

N;N

REVEL

Benign

0.0040

Sift

Benign

0.43

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.13

.;B

Vest4

0.064

MutPred

0.34

.;Gain of ubiquitination at K483 (P = 0.0931);

MVP

0.11

MPC

0.095

ClinPred

0.057

GERP RS

-1.4

Varity_R

0.046

gMVP

0.0081

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