chr19-12527522-G-A

Position:

• chr19-12527522-G-A

Variant summary

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

The NM_144976.4(ZNF564):​c.586C>T​(p.Pro196Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF564 NM_144976.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.556

Genes affected

ZNF564 (HGNC:31106): (zinc finger protein 564) Predicted to enable DNA-binding transcription factor activity 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 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=0.23684743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF564	NM_144976.4	c.586C>T	p.Pro196Ser	missense_variant	4/4	ENST00000339282.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF564	ENST00000339282.12	c.586C>T	p.Pro196Ser	missense_variant	4/4	1	NM_144976.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.0	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	N
PROVEAN	Pathogenic	-6.7	D
REVEL	Benign	0.041
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.13
MutPred		0.52		Gain of MoRF binding (P = 0.0682);
MVP		0.19
MPC		0.65
ClinPred		0.96	D
GERP RS		-0.61
Varity_R		0.30
gMVP		0.016

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: chr19-12638336;