Variant chr19-36183160-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_152477.5(ZNF565):c.806A>T(p.His269Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF565
NM_152477.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.40

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.966

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF565	NM_152477.5 linkuse as main transcript	c.806A>T	p.His269Leu	missense_variant	5/5	ENST00000304116.10	NP_689690.3	Q8N9K5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF565	ENST00000304116.10 linkuse as main transcript	c.806A>T	p.His269Leu	missense_variant	5/5	2	NM_152477.5	ENSP00000306869.5	Q8N9K5-2
ZNF565	ENST00000591473.1 linkuse as main transcript	c.611A>T	p.His204Leu	missense_variant	4/4	1		ENSP00000465906.1	K7EL42
ZNF565	ENST00000355114.9 linkuse as main transcript	c.926A>T	p.His309Leu	missense_variant	5/5	2		ENSP00000347234.5	Q8N9K5-1
ZNF565	ENST00000392173.6 linkuse as main transcript	c.806A>T	p.His269Leu	missense_variant	5/5	2		ENSP00000376013.1	Q8N9K5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.806A>T (p.H269L) alteration is located in exon 5 (coding exon 4) of the ZNF565 gene. This alteration results from a A to T substitution at nucleotide position 806, causing the histidine (H) at amino acid position 269 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.30

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.37

.;.;T;.

Eigen

Pathogenic

0.77

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.57

T;.;T;T

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.97

D;D;D;D

MetaSVM

Pathogenic

0.98

MutationAssessor

Pathogenic

4.3

H;H;.;.

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-11

D;D;D;.

REVEL

Uncertain

0.62

Sift

Pathogenic

0.0

D;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;.

Vest4

0.70

MutPred

0.77

Loss of disorder (P = 0.0458);Loss of disorder (P = 0.0458);.;.;

MVP

0.98

MPC

1.3

ClinPred

1.0

GERP RS

4.4

Varity_R

0.91

gMVP

0.32

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over