chr1-52813521-C-CT

Position:

• chr1-52813521-C-CT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_024646.3(ZYG11B):​c.1696-5dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00865 in 1,314,736 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00076 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0097 (0 hom.)
• Consequence: ZYG11B NM_024646.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.460

Genes affected

ZYG11B (HGNC:25820): (zyg-11 family member B, cell cycle regulator) Involved in positive regulation of proteasomal ubiquitin-dependent protein catabolic process and protein quality control for misfolded or incompletely synthesized proteins. Part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 1-52813521-C-CT is Benign according to our data. Variant chr1-52813521-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 3060468.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 114 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZYG11B	NM_024646.3	c.1696-5dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000294353.7
ZYG11B	XM_006710898.5	c.1684-5dup		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZYG11B	ENST00000294353.7	c.1696-5dup		splice_polypyrimidine_tract_variant, intron_variant		1	NM_024646.3	P1
ZYG11B	ENST00000545132.5	c.*49-5dup		splice_polypyrimidine_tract_variant, intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.000762 AC: 114 AN: 149546 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00233

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.000298

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000104

Gnomad OTH AF: 0.00147

GnomAD4 exome AF: 0.00966 AC: 11260 AN: 1165094 Hom.: 0 Cov.: 27 AF XY: 0.00921 AC XY: 5330 AN XY: 578788

Gnomad4 AFR exome AF: 0.0121

Gnomad4 AMR exome AF: 0.00893

Gnomad4 ASJ exome AF: 0.00795

Gnomad4 EAS exome AF: 0.00718

Gnomad4 SAS exome AF: 0.00859

Gnomad4 FIN exome AF: 0.00684

Gnomad4 NFE exome AF: 0.0100

Gnomad4 OTH exome AF: 0.00915

GnomAD4 genome AF: 0.000762 AC: 114 AN: 149642 Hom.: 0 Cov.: 32 AF XY: 0.000658 AC XY: 48 AN XY: 72986

Gnomad4 AFR AF: 0.00233

Gnomad4 AMR AF: 0.000268

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000212

Gnomad4 FIN AF: 0.000298

Gnomad4 NFE AF: 0.000104

Gnomad4 OTH AF: 0.00146

Bravo AF: 0.000771

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ZYG11B-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 03, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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: rs760756606; hg19: chr1-53279193;