rs34995077

chr19-36194255-A-Gchr19-36194255-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_152477.5(ZNF565):c.210T>C(p.Asp70=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,612,728 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0093 (25 hom., cov: 32)
  • Exomes 𝑓: 0.00096 (10 hom.)
• Consequence: ZNF565 NM_152477.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

Genes affected

ZNF565 (HGNC:26726): (zinc finger protein 565) 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=0.033 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00928 (1412/152212) while in subpopulation AFR AF= 0.0321 (1332/41524). AF 95% confidence interval is 0.0306. There are 25 homozygotes in gnomad4. There are 661 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1409 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF565	NM_152477.5	c.210T>C	p.Asp70=	synonymous_variant	4/5	ENST00000304116.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF565	ENST00000304116.10	c.210T>C	p.Asp70=	synonymous_variant	4/5	2	NM_152477.5	P1

Frequencies

GnomAD3 genomes AF: 0.00926 AC: 1409 AN: 152094 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00251 AC: 625 AN: 249282 Hom.: 10 AF XY: 0.00183 AC XY: 247 AN XY: 134694

Gnomad AFR exome AF: 0.0315

Gnomad AMR exome AF: 0.00175

Gnomad ASJ exome AF: 0.00302

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000331

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000221

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000959 AC: 1401 AN: 1460516 Hom.: 10 Cov.: 30 AF XY: 0.000833 AC XY: 605 AN XY: 726392

Gnomad4 AFR exome AF: 0.0295

Gnomad4 AMR exome AF: 0.00202

Gnomad4 ASJ exome AF: 0.00327

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000466

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000684

Gnomad4 OTH exome AF: 0.00257

GnomAD4 genome AF: 0.00928 AC: 1412 AN: 152212 Hom.: 25 Cov.: 32 AF XY: 0.00888 AC XY: 661 AN XY: 74438

Gnomad4 AFR AF: 0.0321

Gnomad4 AMR AF: 0.00295

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00546 Hom.: 1

Bravo AF: 0.00999

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	7.3
Dann	Benign	0.70

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: rs34995077; hg19: chr19-36685157;