Variant 19-58246711-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014480.4(ZNF544):c.161G>T(p.Gly54Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ZNF544
NM_014480.4 missense, splice_region

Scores

Splicing: ADA: 0.9697

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.16

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF544	NM_014480.4 link	c.161G>T	p.Gly54Val	missense_variant, splice_region_variant	Exon 6 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.161G>T	p.Gly54Val	missense_variant, splice_region_variant	Exon 6 of 7		NM_014480.4	ENSP00000510489.1		Q6NX49
ENSG00000283515	ENST00000637233.1 link	n.161-35G>T		intron_variant	Intron 5 of 11	5		ENSP00000490395.1		A0A1B0GV72

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251348

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135862

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:

0.000163

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727212

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:

0.0000225

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000795

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.161G>T (p.G54V) alteration is located in exon 6 (coding exon 3) of the ZNF544 gene. This alteration results from a G to T substitution at nucleotide position 161, causing the glycine (G) at amino acid position 54 to be replaced by a valine (V). 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

0.79

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

.;T;.;.;.;T

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.014

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.82

T;.;T;T;T;T

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.53

D;D;D;D;D;D

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.8

.;M;.;.;.;M

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-6.8

.;.;.;.;.;D

REVEL

Benign

0.16

Sift

Pathogenic

0.0

.;.;.;.;.;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D;D

Polyphen

1.0

.;D;.;.;.;D

Vest4

0.57, 0.51, 0.47, 0.56, 0.56

MVP

0.46

MPC

0.18

ClinPred

0.87

GERP RS

1.8

Varity_R

0.59

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.97

dbscSNV1_RF

Pathogenic

0.81

SpliceAI score (max)

0.44

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.24

Position offset: 35

DS_AL_spliceai

0.44

Position offset: 0

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