19-36182582-G-A

Variant names:

• chr19-36182582-G-A
• rs755514378
• NM_152477.5:c.1384C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152477.5(ZNF565):​c.1384C>T​(p.Leu462Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L462V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF565 NM_152477.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 0 publications found

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]

ZNF565 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3399939).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152477.5. 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
	ZNF565	NM_152477.5	MANE Select	c.1384C>T	p.Leu462Phe	missense	Exon 5 of 5	NP_689690.3
	ZNF565	NM_001042474.2		c.1384C>T	p.Leu462Phe	missense	Exon 5 of 5	NP_001035939.1	Q8N9K5-2
	ZNF565	NM_001366188.1		c.1384C>T	p.Leu462Phe	missense	Exon 5 of 5	NP_001353117.1	Q8N9K5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF565	ENST00000304116.10	TSL:2 MANE Select	c.1384C>T	p.Leu462Phe	missense	Exon 5 of 5	ENSP00000306869.5	Q8N9K5-2
	ZNF565	ENST00000355114.9	TSL:2	c.1504C>T	p.Leu502Phe	missense	Exon 5 of 5	ENSP00000347234.5	Q8N9K5-1
	ZNF565	ENST00000392173.6	TSL:2	c.1384C>T	p.Leu462Phe	missense	Exon 5 of 5	ENSP00000376013.1	Q8N9K5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461834 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111972

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.4
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.27
Sift	Benign	0.053	T
Sift4G	Uncertain	0.037	D
Vest4		0.40
MutPred		0.66		Loss of catalytic residue at L462 (P = 0.1187)
MVP		0.72
MPC		1.2
ClinPred		0.95	D
GERP RS		4.8
Varity_R		0.25
gMVP		0.16
Mutation Taster		=96/4	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

dbSNP: rs755514378; hg19: chr19-36673484;