19-52511066-A-G

Variant names:

• chr19-52511066-A-G
• NM_001099694.2:c.685A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099694.2(ZNF578):​c.685A>G​(p.Lys229Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 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)
• Consequence: ZNF578 NM_001099694.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0230
• Publications: 0 publications found

Genes affected

ZNF578 (HGNC:26449): (zinc finger protein 578) 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 located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000269349 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13390556).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099694.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF578	NM_001099694.2	MANE Select	c.685A>G	p.Lys229Glu	missense	Exon 6 of 6	NP_001093164.1	Q96N58
	ZNF578	NM_001366182.2		c.685A>G	p.Lys229Glu	missense	Exon 6 of 6	NP_001353111.1	Q96N58

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF578	ENST00000421239.7	TSL:2 MANE Select	c.685A>G	p.Lys229Glu	missense	Exon 6 of 6	ENSP00000459216.1	Q96N58
	ZNF578	ENST00000601120.1	TSL:5	c.685A>G	p.Lys229Glu	missense	Exon 4 of 4	ENSP00000470790.1	M0QZV4
	ENSG00000269349	ENST00000599143.1	TSL:5	n.*216T>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.023
Sift4G	Uncertain	0.041	D
Vest4		0.061
MVP		0.33
MPC		0.024
ClinPred		0.17	T
GERP RS		0.35
Varity_R		0.13
gMVP		0.020
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

hg19: chr19-53014319;