Variant 19-12391148-G-T 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.1250C>A(p.Ala417Glu) 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 152,190 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

ZNF799
NM_001080821.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0600

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=0.06448078).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF799	NM_001080821.3 linkuse as main transcript	c.1250C>A	p.Ala417Glu	missense_variant	4/4	ENST00000430385.3	NP_001074290.1	Q96GE5-1
ZNF799	NM_001322497.2 linkuse as main transcript	c.1154C>A	p.Ala385Glu	missense_variant	4/4		NP_001309426.1	D3YTF2
ZNF799	NM_001322498.2 linkuse as main transcript	c.1154C>A	p.Ala385Glu	missense_variant	5/5		NP_001309427.1	D3YTF2
ZNF799	XM_047439649.1 linkuse as main transcript	c.1250C>A	p.Ala417Glu	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.1250C>A	p.Ala417Glu	missense_variant	4/4	2	NM_001080821.3	ENSP00000411084.2	Q96GE5-1
ZNF799	ENST00000460935.1 linkuse as main transcript	n.2944C>A		non_coding_transcript_exon_variant	3/3	1
ZNF799	ENST00000419318.5 linkuse as main transcript	c.1154C>A	p.Ala385Glu	missense_variant	4/4	2		ENSP00000415278.1	D3YTF2
ENSG00000268744	ENST00000435033.1 linkuse as main transcript	n.208-7461C>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152190

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74358

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:

0.0000113

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

Dec 14, 2023

The c.1250C>A (p.A417E) alteration is located in exon 4 (coding exon 4) of the ZNF799 gene. This alteration results from a C to A substitution at nucleotide position 1250, causing the alanine (A) at amino acid position 417 to be replaced by a glutamic acid (E). 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

0.17

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.027

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.040

T;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.064

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.43

.;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.032

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.46

.;P

Vest4

0.17

MutPred

0.40

.;Gain of ubiquitination at K413 (P = 0.0419);

MVP

0.19

MPC

0.17

ClinPred

0.21

GERP RS

-2.3

Varity_R

0.20

gMVP

0.0092

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