19-36182677-C-G

Variant names:

• chr19-36182677-C-G
• rs375467058
• NM_152477.5:c.1289G>C

Variant summary

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

The NM_152477.5(ZNF565):​c.1289G>C​(p.Arg430Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,146 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. R430H) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ZNF565 NM_152477.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13898808).

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.1289G>C	p.Arg430Pro	missense	Exon 5 of 5	NP_689690.3
	ZNF565	NM_001042474.2		c.1289G>C	p.Arg430Pro	missense	Exon 5 of 5	NP_001035939.1	Q8N9K5-2
	ZNF565	NM_001366188.1		c.1289G>C	p.Arg430Pro	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.1289G>C	p.Arg430Pro	missense	Exon 5 of 5	ENSP00000306869.5	Q8N9K5-2
	ZNF565	ENST00000355114.9	TSL:2	c.1409G>C	p.Arg470Pro	missense	Exon 5 of 5	ENSP00000347234.5	Q8N9K5-1
	ZNF565	ENST00000392173.6	TSL:2	c.1289G>C	p.Arg430Pro	missense	Exon 5 of 5	ENSP00000376013.1	Q8N9K5-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74322

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.096	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-0.48
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.12
Sift	Benign	0.20	T
Sift4G	Benign	0.14	T
Vest4		0.23
MutPred		0.42		Loss of MoRF binding (P = 0.0078)
MVP		0.40
MPC		1.4
ClinPred		0.88	D
GERP RS		1.4
Varity_R		0.53
gMVP		0.42
Mutation Taster		=95/5	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: rs375467058; hg19: chr19-36673579;