1-52757822-G-A

Variant names:

• chr1-52757822-G-A
• rs6588441
• NM_024646.3:c.196+1199G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024646.3(ZYG11B):​c.196+1199G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,006 control chromosomes in the GnomAD database, including 29,431 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 0.59 (29431 hom., cov: 31)
• Consequence: ZYG11B NM_024646.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024646.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZYG11B	NM_024646.3	MANE Select	c.196+1199G>A		intron	N/A	NP_078922.1	Q9C0D3-1
	ZYG11B	NM_001441954.1		c.184+1199G>A		intron	N/A	NP_001428883.1
	ZYG11B	NR_199864.1		n.397+1199G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZYG11B	ENST00000294353.7	TSL:1 MANE Select	c.196+1199G>A		intron	N/A	ENSP00000294353.6	Q9C0D3-1
	ZYG11B	ENST00000884648.1		c.193+1199G>A		intron	N/A	ENSP00000554707.1
	ZYG11B	ENST00000959293.1		c.196+1199G>A		intron	N/A	ENSP00000629352.1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89948 AN: 151888 Hom.: 29352 Cov.: 31

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.551

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.593 AC: 90095 AN: 152006 Hom.: 29431 Cov.: 31 AF XY: 0.598 AC XY: 44456 AN XY: 74296

African (AFR) AF: 0.840 AC: 34840 AN: 41480

American (AMR) AF: 0.632 AC: 9638 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1881 AN: 3470

East Asian (EAS) AF: 0.972 AC: 5022 AN: 5168

South Asian (SAS) AF: 0.491 AC: 2365 AN: 4818

European-Finnish (FIN) AF: 0.502 AC: 5289 AN: 10540

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29278 AN: 67952

Other (OTH) AF: 0.557 AC: 1178 AN: 2114

Alfa AF: 0.526 Hom.: 2982

Bravo AF: 0.618

Asia WGS AF: 0.766 AC: 2664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.91
DANN	Benign	0.22
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6588441; hg19: chr1-53223494;