10-122836358-GAAAAAAA-GAAAA

Variant names:

• chr10-122836358-GAAA-G
• rs11365591
• NM_022034.6:c.818-11_818-9delTTT

Variant summary

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

The NM_022034.6(CUZD1):​c.818-11_818-9delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,157,668 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 0.00012 (0 hom., cov: 0)
  • Exomes 𝑓: 0.019 (0 hom.)
• Consequence: CUZD1 NM_022034.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233
• 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 AMR (0.0428) population. However there is too low homozygotes in high coverage region: (expected more than 81, got 0).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUZD1	NM_022034.6	c.818-11_818-9delTTT		intron_variant	Intron 5 of 8	ENST00000392790.6	NP_071317.2
CUZD1	NR_037912.2	n.681-11_681-9delTTT		intron_variant	Intron 4 of 7
FAM24B-CUZD1	NR_037915.1	n.1494-11_1494-9delTTT		intron_variant	Intron 7 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUZD1	ENST00000392790.6	c.818-11_818-9delTTT		intron_variant	Intron 5 of 8	1	NM_022034.6	ENSP00000376540.1
ENSG00000286088	ENST00000368904.6	n.818-11_818-9delTTT		intron_variant	Intron 6 of 9	1		ENSP00000357900.2

Frequencies

GnomAD3 genomes AF: 0.000121 AC: 17 AN: 140974 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000523

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000141

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000251

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000154

Gnomad OTH AF: 0.000522

GnomAD2 exomes AF: 0.0589 AC: 4185 AN: 71052 AF XY: 0.0608

Gnomad AFR exome AF: 0.0559

Gnomad AMR exome AF: 0.0643

Gnomad ASJ exome AF: 0.0518

Gnomad EAS exome AF: 0.0652

Gnomad FIN exome AF: 0.0500

Gnomad NFE exome AF: 0.0585

Gnomad OTH exome AF: 0.0587

GnomAD4 exome AF: 0.0191 AC: 19370 AN: 1016690 Hom.: 0 AF XY: 0.0203 AC XY: 10137 AN XY: 498660

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

African (AFR) AF: 0.0185 AC: 387 AN: 20968

American (AMR) AF: 0.0455 AC: 710 AN: 15590

Ashkenazi Jewish (ASJ) AF: 0.0255 AC: 403 AN: 15806

East Asian (EAS) AF: 0.0246 AC: 673 AN: 27320

South Asian (SAS) AF: 0.0408 AC: 1836 AN: 45046

European-Finnish (FIN) AF: 0.0322 AC: 1021 AN: 31690

Middle Eastern (MID) AF: 0.0245 AC: 84 AN: 3434

European-Non Finnish (NFE) AF: 0.0165 AC: 13424 AN: 814766

Other (OTH) AF: 0.0198 AC: 832 AN: 42070

⚠️ 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: 0.000121 AC: 17 AN: 140978 Hom.: 0 Cov.: 0 AF XY: 0.000132 AC XY: 9 AN XY: 67994

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

African (AFR) AF: 0.0000522 AC: 2 AN: 38306

American (AMR) AF: 0.000141 AC: 2 AN: 14218

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4852

South Asian (SAS) AF: 0.00 AC: 0 AN: 4386

European-Finnish (FIN) AF: 0.000251 AC: 2 AN: 7970

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

European-Non Finnish (NFE) AF: 0.000154 AC: 10 AN: 64798

Other (OTH) AF: 0.000519 AC: 1 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.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23
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;