Variant 19-36183430-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_152477.5(ZNF565):c.536G>A(p.Gly179Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ZNF565
NM_152477.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.616

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07890898).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF565	NM_152477.5 linkuse as main transcript	c.536G>A	p.Gly179Asp	missense_variant	5/5	ENST00000304116.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF565	ENST00000304116.10 linkuse as main transcript	c.536G>A	p.Gly179Asp	missense_variant	5/5	2	NM_152477.5	P1	Q8N9K5-2
ZNF565	ENST00000591473.1 linkuse as main transcript	c.341G>A	p.Gly114Asp	missense_variant	4/4	1
ZNF565	ENST00000355114.9 linkuse as main transcript	c.656G>A	p.Gly219Asp	missense_variant	5/5	2			Q8N9K5-1
ZNF565	ENST00000392173.6 linkuse as main transcript	c.536G>A	p.Gly179Asp	missense_variant	5/5	2		P1	Q8N9K5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251462

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000411

AC:

AN:

1459568

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

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, 2024

The c.536G>A (p.G179D) alteration is located in exon 5 (coding exon 4) of the ZNF565 gene. This alteration results from a G to A substitution at nucleotide position 536, causing the glycine (G) at amino acid position 179 to be replaced by an aspartic acid (D). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.86

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.042

T;.;T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.079

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.2

L;L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.4

N;N;N;.

REVEL

Benign

0.070

Sift

Benign

0.62

T;T;T;.

Sift4G

Benign

0.10

T;T;T;.

Vest4

0.22

MutPred

0.23

Loss of MoRF binding (P = 0.0434);Loss of MoRF binding (P = 0.0434);.;.;

MVP

0.35

MPC

0.65

ClinPred

0.17

GERP RS

3.3

Varity_R

0.037

gMVP

0.083

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