chr19-9467851-G-T

Variant names:

• chr19-9467851-G-T
• rs193920939
• NM_152476.3:c.1096C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152476.3(ZNF560):​c.1096C>A​(p.His366Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF560 NM_152476.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.80
• Publications: 1 publications found

Genes affected

ZNF560 (HGNC:26484): (zinc finger protein 560) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.858

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF560	NM_152476.3	c.1096C>A	p.His366Asn	missense_variant	Exon 10 of 10	ENST00000301480.5	NP_689689.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF560	ENST00000301480.5	c.1096C>A	p.His366Asn	missense_variant	Exon 10 of 10	1	NM_152476.3	ENSP00000301480.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer Uncertain:1

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Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	-0.077
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0035	T
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	-0.00070	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		4.8
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.25
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.020	D
Polyphen		0.99	D
Vest4		0.48
MutPred		0.71		Loss of catalytic residue at H366 (P = 0.0054);
MVP		0.89
MPC		0.23
ClinPred		0.94	D
GERP RS		0.70
Varity_R		0.26
gMVP		0.12
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: rs193920939; hg19: chr19-9578527; COSMIC: COSV56872149; COSMIC: COSV56872149;