10-122836358-GAAAAAAA-GA

Variant names:

• chr10-122836358-GAAAAAA-G
• rs11365591
• NM_022034.6:c.818-14_818-9delTTTTTT

Variant summary

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

The NM_022034.6(CUZD1):​c.818-14_818-9delTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 1,067,624 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: not found (cov: 0)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: CUZD1 NM_022034.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 0 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: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUZD1	NM_022034.6	c.818-14_818-9delTTTTTT		intron_variant	Intron 5 of 8	ENST00000392790.6	NP_071317.2
CUZD1	NR_037912.2	n.681-14_681-9delTTTTTT		intron_variant	Intron 4 of 7
FAM24B-CUZD1	NR_037915.1	n.1494-14_1494-9delTTTTTT		intron_variant	Intron 7 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUZD1	ENST00000392790.6	c.818-14_818-9delTTTTTT		intron_variant	Intron 5 of 8	1	NM_022034.6	ENSP00000376540.1
ENSG00000286088	ENST00000368904.6	n.818-14_818-9delTTTTTT		intron_variant	Intron 6 of 9	1		ENSP00000357900.2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000197 AC: 21 AN: 1067624 Hom.: 0 AF XY: 0.0000248 AC XY: 13 AN XY: 523612

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

African (AFR) AF: 0.00 AC: 0 AN: 22122

American (AMR) AF: 0.000122 AC: 2 AN: 16390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16702

East Asian (EAS) AF: 0.00 AC: 0 AN: 29118

South Asian (SAS) AF: 0.000107 AC: 5 AN: 46774

European-Finnish (FIN) AF: 0.000178 AC: 6 AN: 33648

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3634

European-Non Finnish (NFE) AF: 0.00000819 AC: 7 AN: 854814

Other (OTH) AF: 0.0000225 AC: 1 AN: 44422

⚠️ 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 Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs11365591; hg19: chr10-124595874;