19-12390834-G-C

Position:

• chr19-12390834-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001080821.3(ZNF799):​c.1564C>G​(p.His522Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF799 NM_001080821.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.50

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.802

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF799	NM_001080821.3	c.1564C>G	p.His522Asp	missense_variant	4/4	ENST00000430385.3	NP_001074290.1
ZNF799	NM_001322497.2	c.1468C>G	p.His490Asp	missense_variant	4/4		NP_001309426.1
ZNF799	NM_001322498.2	c.1468C>G	p.His490Asp	missense_variant	5/5		NP_001309427.1
ZNF799	XM_047439649.1	c.1564C>G	p.His522Asp	missense_variant	4/4		XP_047295605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF799	ENST00000430385.3	c.1564C>G	p.His522Asp	missense_variant	4/4	2	NM_001080821.3	ENSP00000411084.2
ZNF799	ENST00000460935.1	n.3258C>G		non_coding_transcript_exon_variant	3/3	1
ZNF799	ENST00000419318.5	c.1468C>G	p.His490Asp	missense_variant	4/4	2		ENSP00000415278.1
ENSG00000268744	ENST00000435033.1	n.208-7147C>G		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.1564C>G (p.H522D) 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 1564, causing the histidine (H) at amino acid position 522 to be replaced by an aspartic acid (D). 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	0.93
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.44	.;T
Eigen	Uncertain	0.27
Eigen_PC	Benign	-0.047
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.0038	T
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Pathogenic	3.8	.;H
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-8.0	D;D
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.99	.;D
Vest4		0.33
MutPred		0.79		.;Gain of ubiquitination at K520 (P = 0.0337);
MVP		0.92
MPC		0.54
ClinPred		1.0	D
GERP RS		1.1
Varity_R		0.64
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-12501648;