Variant chr10-122836335-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_022034.6(CUZD1):c.833C>T(p.Ser278Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000782 in 1,522,212 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000065 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000080 ( 1 hom. )

Consequence

CUZD1
NM_022034.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.622

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:

CUZD1 (HGNC:):

CUZD1 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
CUZD1	NM_022034.6 linkuse as main transcript	c.833C>T	p.Ser278Phe	missense_variant	6/9	ENST00000392790.6	NP_071317.2	Q86UP6-1
CUZD1	NR_037912.2 linkuse as main transcript	n.696C>T		non_coding_transcript_exon_variant	5/8
FAM24B-CUZD1	NR_037915.1 linkuse as main transcript	n.1509C>T		non_coding_transcript_exon_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUZD1	ENST00000392790.6 linkuse as main transcript	c.833C>T	p.Ser278Phe	missense_variant	6/9	1	NM_022034.6	ENSP00000376540.1		Q86UP6-1
ENSG00000286088	ENST00000368904.6 linkuse as main transcript	n.833C>T		non_coding_transcript_exon_variant	7/10	1		ENSP00000357900.2		A0A499FIG0

Frequencies

GnomAD3 genomes

AF:

0.0000647

AC:

AN:

139206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000272

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000106

Gnomad OTH

AF:

0.000545

GnomAD4 exome

AF:

0.0000795

AC:

110

AN:

1383006

Hom.:

Cov.:

AF XY:

0.0000904

AC XY:

AN XY:

686000

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000101

Gnomad4 OTH exome

AF:

0.0000176

GnomAD4 genome

AF:

0.0000647

AC:

AN:

139206

Hom.:

Cov.:

AF XY:

0.0000600

AC XY:

AN XY:

66676

show subpopulations

Gnomad4 AFR

AF:

0.0000272

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000106

Gnomad4 OTH

AF:

0.000545

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2024

The c.833C>T (p.S278F) alteration is located in exon 6 (coding exon 6) of the CUZD1 gene. This alteration results from a C to T substitution at nucleotide position 833, causing the serine (S) at amino acid position 278 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.31

T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.68

.;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.36

MutationAssessor

Benign

1.5

L;L

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.19

Sift

Benign

0.58

T;T

Sift4G

Benign

0.081

T;T

Polyphen

0.063

B;B

Vest4

0.14

MVP

0.82

MPC

0.084

ClinPred

0.10

GERP RS

2.1

Varity_R

0.035

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.23

Position offset: 15

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over