Genetic Variant ZYG11B:c.1696-5delT (chr1-52813521-CT-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_024646.3(ZYG11B):c.1696-5delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000959 in 1,380,618 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000074 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

ZYG11B
NM_024646.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.460

Variant links:

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]

ZYG11B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZYG11B	NM_024646.3 link	c.1696-5delT		splice_region_variant, intron_variant	Intron 10 of 13	ENST00000294353.7	NP_078922.1	Q9C0D3-1B4DK95
ZYG11B	XM_006710898.5 link	c.1684-5delT		splice_region_variant, intron_variant	Intron 10 of 13		XP_006710961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZYG11B	ENST00000294353.7 link	c.1696-14delT		intron_variant	Intron 10 of 13	1	NM_024646.3	ENSP00000294353.6		Q9C0D3-1
ZYG11B	ENST00000545132.5 link	c.*49-14delT		intron_variant	Intron 11 of 13	2		ENSP00000441315.1		A8DPD7

Frequencies

GnomAD3 genomes

AF:

0.0000735

AC:

AN:

149578

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000982

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000670

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000581

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000446

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00107

AC:

1313

AN:

1231040

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

654

AN XY:

611910

show subpopulations

Gnomad4 AFR exome

AF:

0.00126

Gnomad4 AMR exome

AF:

0.00291

Gnomad4 ASJ exome

AF:

0.00103

Gnomad4 EAS exome

AF:

0.00150

Gnomad4 SAS exome

AF:

0.00158

Gnomad4 FIN exome

AF:

0.00136

Gnomad4 NFE exome

AF:

0.000942

Gnomad4 OTH exome

AF:

0.000793

GnomAD4 genome

AF:

0.0000735

AC:

AN:

149578

Hom.:

Cov.:

AF XY:

0.0000960

AC XY:

AN XY:

72892

show subpopulations

Gnomad4 AFR

AF:

0.0000982

Gnomad4 AMR

AF:

0.0000670

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000446

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00496

Hom.:

Bravo

AF:

0.000132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over