Genetic Variant NM_014480.4:c.11G>C (chr19-58244034-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_014480.4(ZNF544):c.11G>C(p.Arg4Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,608,342 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF544
NM_014480.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.28

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:

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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=0.09674385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF544	NM_014480.4 link	c.11G>C	p.Arg4Pro	missense_variant	Exon 4 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.11G>C	p.Arg4Pro	missense_variant	Exon 4 of 7		NM_014480.4	ENSP00000510489.1		Q6NX49
ENSG00000283515	ENST00000637233.1 link	n.11G>C		non_coding_transcript_exon_variant	Exon 4 of 12	5		ENSP00000490395.1		A0A1B0GV72

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152100

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1456242

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724218

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74282

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.023

DANN

Benign

0.85

DEOGEN2

Benign

0.0017

.;.;.;.;T;T;T;.;.;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.65

.;T;.;T;.;.;T;T;T;T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.097

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.52

.;.;.;.;N;.;.;.;.;.;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.29

.;.;.;.;.;.;.;.;.;.;N

REVEL

Benign

0.0060

Sift

Benign

0.042

.;.;.;.;.;.;.;.;.;.;D

Sift4G

Benign

0.23

T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.74

.;.;.;.;P;.;.;.;.;.;P

Vest4

0.10

MutPred

0.35

Loss of methylation at R4 (P = 0.0306);Loss of methylation at R4 (P = 0.0306);Loss of methylation at R4 (P = 0.0306);Loss of methylation at R4 (P = 0.0306);Loss of methylation at R4 (P = 0.0306);Loss of methylation at R4 (P = 0.0306);Loss of methylation at R4 (P = 0.0306);Loss of methylation at R4 (P = 0.0306);Loss of methylation at R4 (P = 0.0306);Loss of methylation at R4 (P = 0.0306);Loss of methylation at R4 (P = 0.0306);

MVP

0.17

MPC

0.023

ClinPred

0.085

GERP RS

-1.5

Varity_R

0.087

gMVP

0.17

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over