chr19-55578836-C-G

Position:

• chr19-55578836-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152600.3(ZNF579):​c.804G>C​(p.Lys268Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF579 NM_152600.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.463

Genes affected

ZNF579 (HGNC:26646): (zinc finger protein 579) Enables RNA binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.24606118).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF579	NM_152600.3	c.804G>C	p.Lys268Asn	missense_variant	2/2	ENST00000325421.7	NP_689813.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF579	ENST00000325421.7	c.804G>C	p.Lys268Asn	missense_variant	2/2	2	NM_152600.3	ENSP00000320188	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

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

Dec 02, 2022

The c.804G>C (p.K268N) alteration is located in exon 2 (coding exon 1) of the ZNF579 gene. This alteration results from a G to C substitution at nucleotide position 804, causing the lysine (K) at amino acid position 268 to be replaced by an asparagine (N). 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	0.98
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.090	T
Eigen	Benign	-0.071
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.51	T
M_CAP	Pathogenic	0.43	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	0.77	N
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.077
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.13	T
Polyphen		0.95	P
Vest4		0.20
MutPred		0.32		Loss of methylation at K268 (P = 0.0013);
MVP		0.48
ClinPred		0.70	D
GERP RS		2.0
Varity_R		0.30
gMVP		0.80

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: chr19-56090202;