chr19-55579122-G-C

Position:

• chr19-55579122-G-C

Variant summary

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

The NM_152600.3(ZNF579):​c.518C>G​(p.Thr173Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000509 in 1,374,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000051 (0 hom.)
• Consequence: ZNF579 NM_152600.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.727

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 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=0.053011477).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF579	NM_152600.3	c.518C>G	p.Thr173Arg	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.518C>G	p.Thr173Arg	missense_variant	2/2	2	NM_152600.3	ENSP00000320188	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000509 AC: 7 AN: 1374076 Hom.: 0 Cov.: 35 AF XY: 0.00000590 AC XY: 4 AN XY: 678106

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: 0.00000651

Gnomad4 OTH exome AF: 0.00

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

Jan 31, 2023

The c.518C>G (p.T173R) alteration is located in exon 2 (coding exon 1) of the ZNF579 gene. This alteration results from a C to G substitution at nucleotide position 518, causing the threonine (T) at amino acid position 173 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	0.20
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	15
DANN	Benign	0.23
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.90	N
REVEL	Benign	0.10
Sift	Benign	0.47	T
Sift4G	Uncertain	0.039	D
Polyphen		0.010	B
Vest4		0.19
MutPred		0.23		Loss of glycosylation at T173 (P = 0.0281);
MVP		0.11
ClinPred		0.028	T
GERP RS		1.2
Varity_R		0.034
gMVP		0.42

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: chr19-56090488;