Variant 19-43597140-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145347.2(ZNF576):c.32A>C(p.Lys11Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,978 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

ZNF576
NM_001145347.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.26

Variant links:

Genes affected

ZNF576 (HGNC:28357): (zinc finger protein 576) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and 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]

ZNF576 links:

SRRM5 (HGNC:37248): (serine/arginine repetitive matrix 5)

SRRM5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.084215164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF576	NM_001145347.2 linkuse as main transcript	c.32A>C	p.Lys11Thr	missense_variant	2/3	ENST00000336564.5	NP_001138819.1
ZNF576	NM_024327.2 linkuse as main transcript	c.32A>C	p.Lys11Thr	missense_variant	2/3		NP_077303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF576	ENST00000336564.5 linkuse as main transcript	c.32A>C	p.Lys11Thr	missense_variant	2/3	1	NM_001145347.2	ENSP00000337852	P1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251444

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727224

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:

0.0000315

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.0000113

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

May 06, 2022

The c.32A>C (p.K11T) alteration is located in exon 2 (coding exon 1) of the ZNF576 gene. This alteration results from a A to C substitution at nucleotide position 32, causing the lysine (K) at amino acid position 11 to be replaced by a threonine (T). 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

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0025

T;T;T;T;T;T

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.52

.;.;.;.;.;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.084

T;T;T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.0

N;N;N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N;D

PrimateAI

Benign

0.38

PROVEAN

Benign

0.10

N;N;N;N;N;N

REVEL

Benign

0.083

Sift

Uncertain

0.012

D;D;D;D;D;D

Sift4G

Benign

0.40

T;T;T;T;T;T

Polyphen

0.0010

B;B;B;B;B;B

Vest4

0.32

MutPred

0.17

Loss of ubiquitination at K11 (P = 0.0034);Loss of ubiquitination at K11 (P = 0.0034);Loss of ubiquitination at K11 (P = 0.0034);Loss of ubiquitination at K11 (P = 0.0034);Loss of ubiquitination at K11 (P = 0.0034);Loss of ubiquitination at K11 (P = 0.0034);

MVP

0.35

MPC

0.66

ClinPred

0.29

GERP RS

3.0

Varity_R

0.079

gMVP

0.21

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