19-58260939-G-C

Variant names:

• chr19-58260939-G-C
• NM_014480.4:c.333G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014480.4(ZNF544):​c.333G>C​(p.Arg111Ser) 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. 15/21 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: -0.721

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 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=0.06372458).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF544	NM_014480.4	c.333G>C	p.Arg111Ser	missense_variant	Exon 7 of 7	ENST00000687789.1	NP_055295.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF544	ENST00000687789.1	c.333G>C	p.Arg111Ser	missense_variant	Exon 7 of 7		NM_014480.4	ENSP00000510489.1
ENSG00000283515	ENST00000637233.1	n.209+14145G>C		intron_variant	Intron 6 of 11	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

Jun 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.333G>C (p.R111S) alteration is located in exon 7 (coding exon 4) of the ZNF544 gene. This alteration results from a G to C substitution at nucleotide position 333, causing the arginine (R) at amino acid position 111 to be replaced by a serine (S). 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	0.16
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.056
DANN	Benign	0.47
DEOGEN2	Benign	0.0095	T;T;T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00028	N
LIST_S2	Benign	0.42	.;.;T;T
M_CAP	Benign	0.00093	T
MetaRNN	Benign	0.064	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.34	N;.;.;N
PrimateAI	Benign	0.17	T
PROVEAN	Benign	-1.6	.;.;.;N
REVEL	Benign	0.011
Sift	Benign	0.12	.;.;.;T
Sift4G	Benign	0.40	T;T;T;T
Polyphen		0.015	B;.;.;B
Vest4		0.081
MutPred		0.23		Gain of phosphorylation at R111 (P = 0.0176);.;.;Gain of phosphorylation at R111 (P = 0.0176);
MVP		0.061
MPC		0.021
ClinPred		0.070	T
GERP RS		-5.0
Varity_R		0.085
gMVP		0.22

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: chr19-58772305; COSMIC: COSV54135853;