19-36997570-C-A

Position:

• chr19-36997570-C-A

Variant summary

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

The NM_001204838.2(ZNF568):​c.1879C>A​(p.Pro627Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,427,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 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: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ZNF568 NM_001204838.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.58

Genes affected

ZNF568 (HGNC:25392): (zinc finger protein 568) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in embryonic placenta morphogenesis and negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000291239 (HGNC:):

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=0.054331064).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF568	NM_001204838.2	c.1879C>A	p.Pro627Thr	missense_variant	10/10		NP_001191767.1
ZNF568	NM_001204839.2	c.1687C>A	p.Pro563Thr	missense_variant	9/9		NP_001191768.1
ZNF568	XM_017026772.2	c.1879C>A	p.Pro627Thr	missense_variant	10/10		XP_016882261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000291239	ENST00000706165.1	c.1879C>A	p.Pro627Thr	missense_variant	12/12			ENSP00000516244.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1427332 Hom.: 0 Cov.: 41 AF XY: 0.00000141 AC XY: 1 AN XY: 708316

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: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.025
DANN	Benign	0.68
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Benign	0.14	T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-0.95	T
PROVEAN	Benign	1.2	N;.
REVEL	Benign	0.033
Sift	Benign	0.25	T;.
Sift4G	Benign	0.36	T;T
Vest4		0.030
MutPred		0.27		Loss of catalytic residue at P563 (P = 0.0977);.;
MVP		0.076
ClinPred		0.066	T
GERP RS		-3.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1644698; hg19: chr19-37488472;