rs375467058

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-36182677-C-A
• chr19-36182677-C-G
• chr19-36182677-C-T

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>T​(p.Arg430Leu) 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. 14/22 in silico tools predict 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: not found (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: 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=0.06153661).

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>T	p.Arg430Leu	missense	Exon 5 of 5	NP_689690.3
	ZNF565	NM_001042474.2		c.1289G>T	p.Arg430Leu	missense	Exon 5 of 5	NP_001035939.1	Q8N9K5-2
	ZNF565	NM_001366188.1		c.1289G>T	p.Arg430Leu	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>T	p.Arg430Leu	missense	Exon 5 of 5	ENSP00000306869.5	Q8N9K5-2
	ZNF565	ENST00000355114.9	TSL:2	c.1409G>T	p.Arg470Leu	missense	Exon 5 of 5	ENSP00000347234.5	Q8N9K5-1
	ZNF565	ENST00000392173.6	TSL:2	c.1289G>T	p.Arg430Leu	missense	Exon 5 of 5	ENSP00000376013.1	Q8N9K5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.72
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.48
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.049
Sift	Benign	0.68	T
Sift4G	Benign	0.72	T
Vest4		0.40
MutPred		0.43		Loss of MoRF binding (P = 0.0174)
MVP		0.10
MPC		0.53
ClinPred		0.061	T
GERP RS		1.4
Varity_R		0.11
gMVP		0.24
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;