NM_152477.5:c.1289G>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152477.5(ZNF565):​c.1289G>A​(p.Arg430His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000867 in 1,614,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000090 (0 hom.)
• Consequence: ZNF565 NM_152477.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03879714).

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>A	p.Arg430His	missense	Exon 5 of 5	NP_689690.3
	ZNF565	NM_001042474.2		c.1289G>A	p.Arg430His	missense	Exon 5 of 5	NP_001035939.1	Q8N9K5-2
	ZNF565	NM_001366188.1		c.1289G>A	p.Arg430His	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>A	p.Arg430His	missense	Exon 5 of 5	ENSP00000306869.5	Q8N9K5-2
	ZNF565	ENST00000355114.9	TSL:2	c.1409G>A	p.Arg470His	missense	Exon 5 of 5	ENSP00000347234.5	Q8N9K5-1
	ZNF565	ENST00000392173.6	TSL:2	c.1289G>A	p.Arg430His	missense	Exon 5 of 5	ENSP00000376013.1	Q8N9K5-2

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

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: 0.0000735

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000716 AC: 18 AN: 251362 AF XY: 0.0000662

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000903 AC: 132 AN: 1461854 Hom.: 0 Cov.: 30 AF XY: 0.0000921 AC XY: 67 AN XY: 727230

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

American (AMR) AF: 0.0000224 AC: 1 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86256

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000112 AC: 124 AN: 1111982

Other (OTH) AF: 0.0000828 AC: 5 AN: 60396

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74322

African (AFR) AF: 0.0000483 AC: 2 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: 0.0000735 AC: 5 AN: 68030

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.0000491

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.000164

EpiControl AF: 0.00

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	Uncertain	0.50
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.48
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.14
Sift	Benign	0.55	T
Sift4G	Benign	0.59	T
Vest4		0.12
MVP		0.095
MPC		0.62
ClinPred		0.027	T
GERP RS		1.4
Varity_R		0.061
gMVP		0.14
Mutation Taster		=98/2	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;