19-36194255-A-T

Position:

• chr19-36194255-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152477.5(ZNF565):​c.210T>A​(p.Asp70Glu) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF565 NM_152477.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

Genes affected

ZNF565 (HGNC:26726): (zinc finger protein 565) 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 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=0.028905481).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF565	NM_152477.5	c.210T>A	p.Asp70Glu	missense_variant	4/5	ENST00000304116.10	NP_689690.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF565	ENST00000304116.10	c.210T>A	p.Asp70Glu	missense_variant	4/5	2	NM_152477.5	ENSP00000306869.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.0
DANN	Benign	0.87
DEOGEN2	Benign	0.0035	.;.;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.11	T;.;T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.029	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.1	N;N;.;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.94	N;N;N;.
REVEL	Benign	0.014
Sift	Benign	1.0	T;T;T;.
Sift4G	Benign	1.0	T;T;T;.
Vest4		0.15
MutPred		0.47		Loss of catalytic residue at A68 (P = 0.2719);Loss of catalytic residue at A68 (P = 0.2719);.;.;
MVP		0.21
MPC		0.36
ClinPred		0.043	T
GERP RS		-4.0
Varity_R		0.030
gMVP		0.014

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

Other links and lift over

dbSNP: rs34995077; hg19: chr19-36685157;