19-57253418-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001023563.4(ZNF805):c.599A>G(p.Glu200Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,410,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ZNF805 NM_001023563.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25

Genes affected

ZNF805 (HGNC:23272): (zinc finger protein 805) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-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]

ACMG classification

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=0.117370546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF805	NM_001023563.4	c.599A>G	p.Glu200Gly	missense_variant	4/4	ENST00000414468.3
ZNF805	NM_001145078.2	c.200A>G	p.Glu67Gly	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF805	ENST00000414468.3	c.599A>G	p.Glu200Gly	missense_variant	4/4	5	NM_001023563.4	P1
ZNF805	ENST00000354309.4	c.200A>G	p.Glu67Gly	missense_variant	3/3	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1410934 Hom.: 0 Cov.: 96 AF XY: 0.00 AC XY: 0 AN XY: 697234

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: 9.21e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Dec 26, 2023

The c.599A>G (p.E200G) alteration is located in exon 4 (coding exon 4) of the ZNF805 gene. This alteration results from a A to G substitution at nucleotide position 599, causing the glutamic acid (E) at amino acid position 200 to be replaced by a glycine (G). 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	0.067
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	18
Dann	Uncertain	0.99
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.021	T;T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.69	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Benign	0.12
Sift	Uncertain	0.013	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.86	.;P
Vest4		0.076
MutPred		0.46		.;Loss of ubiquitination at K204 (P = 0.0474);
MVP		0.19
MPC		0.30
ClinPred		0.53	D
GERP RS		0.76
Varity_R		0.13
gMVP		0.038

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: chr19-57764786;