19-52906633-T-A

Position:

• chr19-52906633-T-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001393938.1(ZNF888):​c.1689A>T​(p.Ser563Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00679 in 1,613,884 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0070 (50 hom.)
• Consequence: ZNF888 NM_001393938.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.50

Genes affected

ZNF888 (HGNC:38695): (zinc finger protein 888) 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 regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-52906633-T-A is Benign according to our data. Variant chr19-52906633-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2650399.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.49 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF888	NM_001393938.1	c.1689A>T	p.Ser563Ser	synonymous_variant	5/5	ENST00000638862.2	NP_001380867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF888	ENST00000638862.2	c.1689A>T	p.Ser563Ser	synonymous_variant	5/5	5	NM_001393938.1	ENSP00000491567.1

Frequencies

GnomAD3 genomes AF: 0.00461 AC: 701 AN: 152166 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00415

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00744

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00702 AC: 10255 AN: 1461600 Hom.: 50 Cov.: 32 AF XY: 0.00695 AC XY: 5052 AN XY: 727096

Gnomad4 AFR exome AF: 0.00122

Gnomad4 AMR exome AF: 0.00110

Gnomad4 ASJ exome AF: 0.0130

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000800

Gnomad4 FIN exome AF: 0.00491

Gnomad4 NFE exome AF: 0.00826

Gnomad4 OTH exome AF: 0.00510

GnomAD4 genome AF: 0.00460 AC: 701 AN: 152284 Hom.: 5 Cov.: 33 AF XY: 0.00407 AC XY: 303 AN XY: 74470

Gnomad4 AFR AF: 0.00144

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00415

Gnomad4 NFE AF: 0.00744

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00490 Hom.: 1

Bravo AF: 0.00457

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

ZNF888: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.61

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

LitVar

Other links and lift over

dbSNP: rs145845241; hg19: chr19-53409886;