Genetic Variant CUZD1:c.818-10_818-9delTT (chr10-122836358-GAA-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_022034.6(CUZD1):c.818-10_818-9delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,095,246 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 0)

Exomes 𝑓: 0.20 ( 0 hom. )

Consequence

CUZD1
NM_022034.6 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.127

Publications

1 publications found

Variant links:

Genes affected

CUZD1 (HGNC:17937): (CUB and zona pellucida like domains 1) Predicted to be involved in trypsinogen activation. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

CUZD1 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

CUZD1 links:

ENSG00000286088 (HGNC:):

ENSG00000286088 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Variant has high frequency in the AMR (0.247) population. However there is too low homozygotes in high coverage region: (expected more than 8623, got 0).

BP6

Variant 10-122836358-GAA-G is Benign according to our data. Variant chr10-122836358-GAA-G is described in ClinVar as Benign. ClinVar VariationId is 402576.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CUZD1	NM_022034.6 link	c.818-10_818-9delTT	intron_variant	Intron 5 of 8	ENST00000392790.6	NP_071317.2	Q86UP6-1
CUZD1	NR_037912.2 link	n.681-10_681-9delTT	intron_variant	Intron 4 of 7
FAM24B-CUZD1	NR_037915.1 link	n.1494-10_1494-9delTT	intron_variant	Intron 7 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUZD1	ENST00000392790.6 link	c.818-10_818-9delTT		intron_variant	Intron 5 of 8	1	NM_022034.6	ENSP00000376540.1		Q86UP6-1
ENSG00000286088	ENST00000368904.6 link	n.818-10_818-9delTT		intron_variant	Intron 6 of 9	1		ENSP00000357900.2		A0A499FIG0

Frequencies

GnomAD3 genomes

AF:

0.00246

AC:

346

AN:

140904

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00247

Gnomad ASJ

AF:

0.00328

Gnomad EAS

AF:

0.00144

Gnomad SAS

AF:

0.00113

Gnomad FIN

AF:

0.00979

Gnomad MID

AF:

0.00336

Gnomad NFE

AF:

0.00236

Gnomad OTH

AF:

0.00470

GnomAD2 exomes

AF:

0.296

AC:

21034

AN:

71052

AF XY:

0.293

show subpopulations

Gnomad AFR exome

AF:

0.300

Gnomad AMR exome

AF:

0.293

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.273

Gnomad FIN exome

AF:

0.285

Gnomad NFE exome

AF:

0.308

Gnomad OTH exome

AF:

0.289

GnomAD4 exome

AF:

0.203

AC:

194023

AN:

954342

Hom.:

AF XY:

0.206

AC XY:

96276

AN XY:

468494

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.206

AC:

4066

AN:

19764

American (AMR)

AF:

0.254

AC:

3819

AN:

15030

Ashkenazi Jewish (ASJ)

AF:

0.232

AC:

3457

AN:

14910

East Asian (EAS)

AF:

0.252

AC:

6226

AN:

24738

South Asian (SAS)

AF:

0.209

AC:

9336

AN:

44586

European-Finnish (FIN)

AF:

0.249

AC:

7373

AN:

29638

Middle Eastern (MID)

AF:

0.218

AC:

714

AN:

3280

European-Non Finnish (NFE)

AF:

0.198

AC:

150702

AN:

762966

Other (OTH)

AF:

0.211

AC:

8330

AN:

39430

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.292

Heterozygous variant carriers

14289

28578

42866

57155

71444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

5532

11064

16596

22128

27660

<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:

0.00249

AC:

351

AN:

140904

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

220

AN XY:

67952

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00131

AC:

AN:

38300

American (AMR)

AF:

0.00246

AC:

AN:

14212

Ashkenazi Jewish (ASJ)

AF:

0.00328

AC:

AN:

3352

East Asian (EAS)

AF:

0.00144

AC:

AN:

4850

South Asian (SAS)

AF:

0.00137

AC:

AN:

4388

European-Finnish (FIN)

AF:

0.00979

AC:

AN:

7966

Middle Eastern (MID)

AF:

0.00368

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.00236

AC:

153

AN:

64744

Other (OTH)

AF:

0.00520

AC:

AN:

1924

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.320

Heterozygous variant carriers

116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over