Variant 19-36183511-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_152477.5(ZNF565):c.455C>T(p.Thr152Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000929 in 1,614,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000096 ( 0 hom. )

Consequence

ZNF565
NM_152477.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.153

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012173533).

BS2

High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF565	NM_152477.5 linkuse as main transcript	c.455C>T	p.Thr152Met	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.455C>T	p.Thr152Met	missense_variant	5/5	2	NM_152477.5	ENSP00000306869.5	Q8N9K5-2
ZNF565	ENST00000591473.1 linkuse as main transcript	c.260C>T	p.Thr87Met	missense_variant	4/4	1		ENSP00000465906.1	K7EL42
ZNF565	ENST00000355114.9 linkuse as main transcript	c.575C>T	p.Thr192Met	missense_variant	5/5	2		ENSP00000347234.5	Q8N9K5-1
ZNF565	ENST00000392173.6 linkuse as main transcript	c.455C>T	p.Thr152Met	missense_variant	5/5	2		ENSP00000376013.1	Q8N9K5-2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000179

AC:

AN:

251466

Hom.:

AF XY:

0.000265

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00144

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000965

AC:

141

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

101

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00133

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000482

Hom.:

ExAC

AF:

0.000165

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Feb 27, 2023

The c.455C>T (p.T152M) alteration is located in exon 5 (coding exon 4) of the ZNF565 gene. This alteration results from a C to T substitution at nucleotide position 455, causing the threonine (T) at amino acid position 152 to be replaced by a methionine (M). 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

Benign

0.096

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.8

DANN

Benign

0.86

DEOGEN2

Benign

0.12

.;.;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.057

T;.;T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.012

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.4

M;M;.;.

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-2.8

D;D;D;.

REVEL

Benign

0.015

Sift

Uncertain

0.023

D;D;D;.

Sift4G

Uncertain

0.014

D;D;D;.

Vest4

0.12

MutPred

0.22

Gain of MoRF binding (P = 0.1071);Gain of MoRF binding (P = 0.1071);.;.;

MVP

0.14

MPC

0.46

ClinPred

0.031

GERP RS

-3.0

Varity_R

0.020

gMVP

0.043

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over