10-122836358-GAAAAAAA-GAAA

Variant names:

• chr10-122836358-GAAAA-G
• rs11365591
• NM_022034.6:c.818-12_818-9delTTTT

Variant summary

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

The NM_022034.6(CUZD1):​c.818-12_818-9delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 1,196,832 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000028 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0023 (0 hom.)
• Consequence: CUZD1 NM_022034.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 1 publications found

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)

ENSG00000286088 (HGNC:):

ACMG classification

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

• PM2: Variant has high frequency in the SAS (0.00644) population. However there is too low homozygotes in high coverage region: (expected more than 1, got 0).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUZD1	NM_022034.6	c.818-12_818-9delTTTT		intron_variant	Intron 5 of 8	ENST00000392790.6	NP_071317.2
CUZD1	NR_037912.2	n.681-12_681-9delTTTT		intron_variant	Intron 4 of 7
FAM24B-CUZD1	NR_037915.1	n.1494-12_1494-9delTTTT		intron_variant	Intron 7 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUZD1	ENST00000392790.6	c.818-12_818-9delTTTT		intron_variant	Intron 5 of 8	1	NM_022034.6	ENSP00000376540.1
ENSG00000286088	ENST00000368904.6	n.818-12_818-9delTTTT		intron_variant	Intron 6 of 9	1		ENSP00000357900.2

Frequencies

GnomAD3 genomes AF: 0.0000284 AC: 4 AN: 141016 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000261

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: 0.000375

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00989 AC: 703 AN: 71052 AF XY: 0.0108

Gnomad AFR exome AF: 0.00643

Gnomad AMR exome AF: 0.0120

Gnomad ASJ exome AF: 0.0127

Gnomad EAS exome AF: 0.0128

Gnomad FIN exome AF: 0.00829

Gnomad NFE exome AF: 0.00907

Gnomad OTH exome AF: 0.00533

GnomAD4 exome AF: 0.00228 AC: 2406 AN: 1055812 Hom.: 0 AF XY: 0.00253 AC XY: 1308 AN XY: 517728

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

African (AFR) AF: 0.00169 AC: 37 AN: 21882

American (AMR) AF: 0.00655 AC: 106 AN: 16182

Ashkenazi Jewish (ASJ) AF: 0.00321 AC: 53 AN: 16486

East Asian (EAS) AF: 0.00261 AC: 75 AN: 28684

South Asian (SAS) AF: 0.00707 AC: 327 AN: 46268

European-Finnish (FIN) AF: 0.00389 AC: 129 AN: 33180

Middle Eastern (MID) AF: 0.00139 AC: 5 AN: 3596

European-Non Finnish (NFE) AF: 0.00186 AC: 1569 AN: 845610

Other (OTH) AF: 0.00239 AC: 105 AN: 43924

⚠️ 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.

GnomAD4 genome AF: 0.0000284 AC: 4 AN: 141020 Hom.: 0 Cov.: 0 AF XY: 0.0000294 AC XY: 2 AN XY: 68020

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

African (AFR) AF: 0.0000261 AC: 1 AN: 38310

American (AMR) AF: 0.00 AC: 0 AN: 14216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3352

East Asian (EAS) AF: 0.00 AC: 0 AN: 4854

South Asian (SAS) AF: 0.00 AC: 0 AN: 4388

European-Finnish (FIN) AF: 0.000375 AC: 3 AN: 7996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 272

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64808

Other (OTH) AF: 0.00 AC: 0 AN: 1928

⚠️ 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.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

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: rs11365591; hg19: chr10-124595874;