rs11365591

chr10-122836358-GAAAAA-Gchr10-122836358-GAAAAA-GAchr10-122836358-GAAAAA-GAAchr10-122836358-GAAAAA-GAAAchr10-122836358-GAAAAA-GAAAAchr10-122836358-GAAAAA-GAAAAAAchr10-122836358-GAAAAA-GAAAAAAAchr10-122836358-GAAAAA-GAAAAAAAAAAAAchr10-122836358-GAAAAA-GAAAAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022034.6(CUZD1):c.818-13_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 0.00022 in 1,206,800 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 0.000014 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: CUZD1 NM_022034.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUZD1	NM_022034.6	c.818-13_818-9del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000392790.6
FAM24B-CUZD1	NR_037915.1	n.1494-13_1494-9del		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant
CUZD1	NR_037912.2	n.681-13_681-9del		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUZD1	ENST00000392790.6	c.818-13_818-9del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_022034.6	P1

Frequencies

GnomAD3 genomes AF: 0.0000142 AC: 2 AN: 141026 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

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: 0.000125

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000154

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000943 AC: 67 AN: 71052 Hom.: 0 AF XY: 0.00111 AC XY: 43 AN XY: 38914

Gnomad AFR exome AF: 0.000779

Gnomad AMR exome AF: 0.000790

Gnomad ASJ exome AF: 0.000408

Gnomad EAS exome AF: 0.000583

Gnomad SAS exome AF: 0.00123

Gnomad FIN exome AF: 0.000553

Gnomad NFE exome AF: 0.00112

Gnomad OTH exome AF: 0.000667

GnomAD4 exome AF: 0.000247 AC: 263 AN: 1065774 Hom.: 0 AF XY: 0.000285 AC XY: 149 AN XY: 522704

Gnomad4 AFR exome AF: 0.000226

Gnomad4 AMR exome AF: 0.000551

Gnomad4 ASJ exome AF: 0.000300

Gnomad4 EAS exome AF: 0.000241

Gnomad4 SAS exome AF: 0.000750

Gnomad4 FIN exome AF: 0.000477

Gnomad4 NFE exome AF: 0.000204

Gnomad4 OTH exome AF: 0.000248

GnomAD4 genome AF: 0.0000142 AC: 2 AN: 141026 Hom.: 0 Cov.: 0 AF XY: 0.0000147 AC XY: 1 AN XY: 67998

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000125

Gnomad4 NFE AF: 0.0000154

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;