Variant 19-58260874-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014480.4(ZNF544):c.268A>C(p.Asn90His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000529 in 1,607,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ZNF544
NM_014480.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.162

Variant links:

Genes affected

ZNF544 (HGNC:16759): (zinc finger protein 544) Predicted to enable DNA-binding transcription activator 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]

ZNF544 links:

ENSG00000283515 (HGNC:):

ENSG00000283515 links:

ZNF8-DT (HGNC:55280): (ZNF8 divergent transcript)

ZNF8-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.011780024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF544	NM_014480.4 link	c.268A>C	p.Asn90His	missense_variant	Exon 7 of 7	ENST00000687789.1	NP_055295.2	Q6NX49

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF544	ENST00000687789.1 link	c.268A>C	p.Asn90His	missense_variant	Exon 7 of 7		NM_014480.4	ENSP00000510489.1		Q6NX49
ENSG00000283515	ENST00000637233.1 link	n.209+14080A>C		intron_variant	Intron 6 of 11	5		ENSP00000490395.1		A0A1B0GV72

Frequencies

GnomAD3 genomes

AF:

0.000323

AC:

AN:

151640

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00119

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000896

AC:

AN:

245512

Hom.:

AF XY:

0.0000527

AC XY:

AN XY:

132710

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.0000301

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:

0.0000254

AC:

AN:

1455298

Hom.:

Cov.:

AF XY:

0.0000263

AC XY:

AN XY:

723610

show subpopulations

Gnomad4 AFR exome

AF:

0.000935

Gnomad4 AMR exome

AF:

0.0000231

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000666

GnomAD4 genome

AF:

0.000316

AC:

AN:

151760

Hom.:

Cov.:

AF XY:

0.000324

AC XY:

AN XY:

74102

show subpopulations

Gnomad4 AFR

AF:

0.00116

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000866

Hom.:

Bravo

AF:

0.000321

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

Asia WGS

AF:

0.000289

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

Oct 21, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.268A>C (p.N90H) alteration is located in exon 7 (coding exon 4) of the ZNF544 gene. This alteration results from a A to C substitution at nucleotide position 268, causing the asparagine (N) at amino acid position 90 to be replaced by a histidine (H). 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

0.11

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.1

DANN

Benign

0.88

DEOGEN2

Benign

0.0046

T;T;T;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.15

.;.;T;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.012

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

L;.;.;L

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.1

.;.;.;N

REVEL

Benign

0.060

Sift

Benign

0.44

.;.;.;T

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.96

D;.;.;D

Vest4

0.14

MVP

0.24

MPC

0.050

ClinPred

0.018

GERP RS

0.78

Varity_R

0.040

gMVP

0.065

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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