10-122836358-GAAAAA-GAA

Position:

• chr10-122836358-GAAAAA-GAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The ENST00000392790.6(CUZD1):​c.818-11_818-9del variant causes a splice polypyrimidine tract, 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 ENST00000392790.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233

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]

FAM24B-CUZD1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0191 (19370/1016690) while in subpopulation AMR AF= 0.0455 (710/15590). AF 95% confidence interval is 0.0428. There are 0 homozygotes in gnomad4_exome. There are 10137 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUZD1	NM_022034.6	c.818-11_818-9del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000392790.6	NP_071317.2
FAM24B-CUZD1	NR_037915.1	n.1494-11_1494-9del		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant
CUZD1	NR_037912.2	n.681-11_681-9del		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUZD1	ENST00000392790.6	c.818-11_818-9del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_022034.6	ENSP00000376540	P1

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

GnomAD3 exomes AF: 0.0589 AC: 4185 AN: 71052 Hom.: 0 AF XY: 0.0608 AC XY: 2366 AN XY: 38914

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 SAS exome AF: 0.0659

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

Gnomad4 AFR exome AF: 0.0185

Gnomad4 AMR exome AF: 0.0455

Gnomad4 ASJ exome AF: 0.0255

Gnomad4 EAS exome AF: 0.0246

Gnomad4 SAS exome AF: 0.0408

Gnomad4 FIN exome AF: 0.0322

Gnomad4 NFE exome AF: 0.0165

Gnomad4 OTH exome AF: 0.0198

GnomAD4 genome AF: 0.000121 AC: 17 AN: 140978 Hom.: 0 Cov.: 0 AF XY: 0.000132 AC XY: 9 AN XY: 67994

Gnomad4 AFR AF: 0.0000522

Gnomad4 AMR AF: 0.000141

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000251

Gnomad4 NFE AF: 0.000154

Gnomad4 OTH AF: 0.000519

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs11365591; hg19: chr10-124595874;