rs193920939

chr19-9467851-G-Achr19-9467851-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152476.3(ZNF560):c.1096C>T(p.His366Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000752 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. H366N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: ZNF560 NM_152476.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.80

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.843

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF560	NM_152476.3	c.1096C>T	p.His366Tyr	missense_variant	10/10	ENST00000301480.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF560	ENST00000301480.5	c.1096C>T	p.His366Tyr	missense_variant	10/10	1	NM_152476.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000120 AC: 3 AN: 250288 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135278

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000752 AC: 11 AN: 1461842 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 727212

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.10
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.30
Eigen_PC	Benign	-0.029
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0029	T
MetaRNN	Pathogenic	0.84	D
MetaSVM	Uncertain	0.069	D
MutationAssessor	Pathogenic	3.5	H
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.38
MutPred		0.78		Gain of phosphorylation at H366 (P = 0.0374);
MVP		0.89
MPC		0.24
ClinPred		0.67	D
GERP RS		0.70
Varity_R		0.32
gMVP		0.15

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

Publications

LitVar

Other links and lift over

dbSNP: rs193920939; hg19: chr19-9578527;