19-58261424-A-G

Position:

• chr19-58261424-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_014480.4(ZNF544):​c.818A>G​(p.Lys273Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: ZNF544 NM_014480.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.130

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]

ENSG00000283515 (HGNC:):

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a cross_link Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) (size 0) in uniprot entity ZN544_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06838179).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF544	NM_014480.4	c.818A>G	p.Lys273Arg	missense_variant	7/7	ENST00000687789.1	NP_055295.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF544	ENST00000687789.1	c.818A>G	p.Lys273Arg	missense_variant	7/7		NM_014480.4	ENSP00000510489.1
ENSG00000283515	ENST00000637233.1	n.209+14630A>G		intron_variant		5		ENSP00000490395.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2021

The c.818A>G (p.K273R) alteration is located in exon 7 (coding exon 4) of the ZNF544 gene. This alteration results from a A to G substitution at nucleotide position 818, causing the lysine (K) at amino acid position 273 to be replaced by an arginine (R). 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	0.080
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.9
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T;T;T;T;T
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.00012	N
LIST_S2	Benign	0.058	T;.;.;T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.068	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	.;N;.;.;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.3	.;.;.;.;N
REVEL	Benign	0.0080
Sift	Benign	0.12	.;.;.;.;T
Sift4G	Uncertain	0.036	D;T;T;T;T
Polyphen		0.11	.;B;.;.;B
Vest4		0.075
MutPred		0.34		.;Loss of methylation at K273 (P = 0.0018);.;.;Loss of methylation at K273 (P = 0.0018);
MVP		0.35
MPC		0.050
ClinPred		0.064	T
GERP RS		1.2
Varity_R		0.034
gMVP		0.0023

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-58772790;