10-122832039-A-G

Variant names:

• chr10-122832039-A-G
• rs7908196
• NM_022034.6:c.*239T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022034.6(CUZD1):​c.*239T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.986 in 379,612 control chromosomes in the GnomAD database, including 184,716 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.99 (74330 hom., cov: 33)
  • Exomes 𝑓: 0.99 (110386 hom.)
• Consequence: CUZD1 NM_022034.6 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUZD1	NM_022034.6	c.*239T>C		downstream_gene_variant		ENST00000392790.6	NP_071317.2
CUZD1	NR_037912.2	n.*119T>C		downstream_gene_variant
FAM24B-CUZD1	NR_037915.1	n.*116T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUZD1	ENST00000392790.6	c.*239T>C		downstream_gene_variant		1	NM_022034.6	ENSP00000376540.1
ENSG00000286088	ENST00000368904.6	n.*1224T>C		downstream_gene_variant		1		ENSP00000357900.2

Frequencies

GnomAD3 genomes AF: 0.988 AC: 150371 AN: 152220 Hom.: 74273 Cov.: 33

Gnomad AFR AF: 0.997

Gnomad AMI AF: 0.958

Gnomad AMR AF: 0.983

Gnomad ASJ AF: 0.998

Gnomad EAS AF: 0.980

Gnomad SAS AF: 0.995

Gnomad FIN AF: 0.990

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.983

Gnomad OTH AF: 0.993

GnomAD4 exome AF: 0.986 AC: 223988 AN: 227274 Hom.: 110386 AF XY: 0.986 AC XY: 117030 AN XY: 118738

African (AFR) AF: 0.997 AC: 7904 AN: 7928

American (AMR) AF: 0.973 AC: 9925 AN: 10196

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 7099 AN: 7110

East Asian (EAS) AF: 0.982 AC: 15990 AN: 16278

South Asian (SAS) AF: 0.995 AC: 22656 AN: 22764

European-Finnish (FIN) AF: 0.991 AC: 12005 AN: 12118

Middle Eastern (MID) AF: 1.00 AC: 990 AN: 990

European-Non Finnish (NFE) AF: 0.983 AC: 134204 AN: 136522

Other (OTH) AF: 0.989 AC: 13215 AN: 13368

GnomAD4 genome AF: 0.988 AC: 150487 AN: 152338 Hom.: 74330 Cov.: 33 AF XY: 0.988 AC XY: 73605 AN XY: 74484

African (AFR) AF: 0.997 AC: 41457 AN: 41578

American (AMR) AF: 0.983 AC: 15054 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 3465 AN: 3472

East Asian (EAS) AF: 0.980 AC: 5075 AN: 5180

South Asian (SAS) AF: 0.995 AC: 4804 AN: 4826

European-Finnish (FIN) AF: 0.990 AC: 10509 AN: 10614

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.983 AC: 66855 AN: 68038

Other (OTH) AF: 0.993 AC: 2100 AN: 2114

Alfa AF: 0.990 Hom.: 15478

Bravo AF: 0.987

Asia WGS AF: 0.993 AC: 3455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.39
DANN	Benign	0.56
PhyloP100		-2.7
Mutation Taster		=98/2	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs7908196; hg19: chr10-124591555;