dbSNP rs760756606: ZYG11B:c.1696-8_1696-5delTTTT (chr1-52813521-CTTTT-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024646.3(ZYG11B):c.1696-8_1696-5delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000287 in 1,392,068 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 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

ZYG11B
NM_024646.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.460

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

multiple congenital anomalies/dysmorphic syndrome
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ZYG11B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZYG11B	NM_024646.3	MANE Select	c.1696-8_1696-5delTTTT	splice_region intron	N/A	NP_078922.1	Q9C0D3-1
ZYG11B	NM_001441954.1		c.1684-8_1684-5delTTTT	splice_region intron	N/A	NP_001428883.1
ZYG11B	NR_199864.1		n.2040-8_2040-5delTTTT	splice_region intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZYG11B	ENST00000294353.7	TSL:1 MANE Select	c.1696-14_1696-11delTTTT	intron	N/A	ENSP00000294353.6	Q9C0D3-1
ZYG11B	ENST00000884648.1		c.1693-14_1693-11delTTTT	intron	N/A	ENSP00000554707.1
ZYG11B	ENST00000959293.1		c.1645-14_1645-11delTTTT	intron	N/A	ENSP00000629352.1

Frequencies

GnomAD3 genomes

AF:

0.00000669

AC:

AN:

149582

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000101

AC:

AN:

99270

AF XY:

0.0000186

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000224

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000241

AC:

AN:

1242390

Hom.:

AF XY:

0.00000162

AC XY:

AN XY:

617674

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27114

American (AMR)

AF:

0.00

AC:

AN:

35874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21656

East Asian (EAS)

AF:

0.00

AC:

AN:

32372

South Asian (SAS)

AF:

0.00

AC:

AN:

70864

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44886

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4970

European-Non Finnish (NFE)

AF:

0.00000315

AC:

AN:

953778

Other (OTH)

AF:

0.00

AC:

AN:

50876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000668

AC:

AN:

149678

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73002

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40846

American (AMR)

AF:

0.00

AC:

AN:

14936

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3432

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67276

Other (OTH)

AF:

0.00

AC:

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over