dbSNP rs1327590386: CUZD1:p.Lys459Asn (chr10-122834711-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022034.6(CUZD1):c.1377G>T(p.Lys459Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CUZD1
NM_022034.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.423

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

CUZD1 links:

ENSG00000286088 (HGNC:):

ENSG00000286088 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17494974).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022034.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CUZD1	NM_022034.6	MANE Select	c.1377G>T	p.Lys459Asn	missense	Exon 7 of 9	NP_071317.2
CUZD1	NR_037912.2		n.1240G>T		non_coding_transcript_exon	Exon 6 of 8
FAM24B-CUZD1	NR_037915.1		n.2053G>T		non_coding_transcript_exon	Exon 9 of 11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CUZD1	ENST00000392790.6	TSL:1 MANE Select	c.1377G>T	p.Lys459Asn	missense	Exon 7 of 9	ENSP00000376540.1	Q86UP6-1
CUZD1	ENST00000338948.3	TSL:1	n.*325G>T		non_coding_transcript_exon	Exon 2 of 4	ENSP00000340905.4	A0A0A0MRA6
CUZD1	ENST00000368899.5	TSL:1	n.1490G>T		non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1443674

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716288

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32714

American (AMR)

AF:

0.00

AC:

AN:

42214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25212

East Asian (EAS)

AF:

0.00

AC:

AN:

39466

South Asian (SAS)

AF:

0.00

AC:

AN:

83242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52960

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5664

European-Non Finnish (NFE)

AF:

9.07e-7

AC:

AN:

1102614

Other (OTH)

AF:

0.00

AC:

AN:

59588

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.66

M_CAP

Benign

0.040

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.6

PhyloP100

-0.42

PROVEAN

Benign

-2.1

REVEL

Benign

0.089

Sift

Benign

0.042

Sift4G

Uncertain

0.010

Polyphen

0.0020

Vest4

0.12

MutPred

0.45

Loss of ubiquitination at K459 (P = 0.0218)

MVP

0.59

MPC

0.075

ClinPred

0.54

GERP RS

1.9

Varity_R

0.11

gMVP

0.21

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over