Genetic Variant CUZD1:c.*239T>C (chr10-122832039-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.66

Variant links:

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 links:

ENSG00000286088 (HGNC:):

ENSG00000286088 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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	Effect	MANE	Protein	UniProt
CUZD1	NM_022034.6 link	c.*239T>C	downstream_gene_variant	ENST00000392790.6	NP_071317.2	Q86UP6-1
CUZD1	NR_037912.2 link	n.*119T>C	downstream_gene_variant
FAM24B-CUZD1	NR_037915.1 link	n.*116T>C	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUZD1	ENST00000392790.6 link	c.*239T>C		downstream_gene_variant		1	NM_022034.6	ENSP00000376540.1		Q86UP6-1
ENSG00000286088	ENST00000368904.6 link	n.*1224T>C		downstream_gene_variant		1		ENSP00000357900.2		A0A499FIG0

Frequencies

GnomAD3 genomes

AF:

0.988

AC:

150371

AN:

152220

Hom.:

74273

Cov.:

show subpopulations

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

show subpopulations

Gnomad4 AFR exome

AF:

0.997

Gnomad4 AMR exome

AF:

0.973

Gnomad4 ASJ exome

AF:

0.998

Gnomad4 EAS exome

AF:

0.982

Gnomad4 SAS exome

AF:

0.995

Gnomad4 FIN exome

AF:

0.991

Gnomad4 NFE exome

AF:

0.983

Gnomad4 OTH exome

AF:

0.989

GnomAD4 genome

AF:

0.988

AC:

150487

AN:

152338

Hom.:

74330

Cov.:

AF XY:

0.988

AC XY:

73605

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.997

Gnomad4 AMR

AF:

0.983

Gnomad4 ASJ

AF:

0.998

Gnomad4 EAS

AF:

0.980

Gnomad4 SAS

AF:

0.995

Gnomad4 FIN

AF:

0.990

Gnomad4 NFE

AF:

0.983

Gnomad4 OTH

AF:

0.993

Alfa

AF:

0.983

Hom.:

9122

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

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over