dbSNP rs36212072: CUZD1:p.Ile285Thr (chr10-122836314-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_022034.6(CUZD1):c.854T>C(p.Ile285Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00743 in 1,604,924 control chromosomes in the GnomAD database, including 46 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 0.0057 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 45 hom. )

Consequence

CUZD1
NM_022034.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.29

Publications

5 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010733813).

BS2

High Homozygotes in GnomAdExome4 at 45 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUZD1	NM_022034.6 link	c.854T>C	p.Ile285Thr	missense_variant	Exon 6 of 9	ENST00000392790.6	NP_071317.2	Q86UP6-1
CUZD1	NR_037912.2 link	n.717T>C		non_coding_transcript_exon_variant	Exon 5 of 8
FAM24B-CUZD1	NR_037915.1 link	n.1530T>C		non_coding_transcript_exon_variant	Exon 8 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CUZD1	ENST00000392790.6 link	c.854T>C	p.Ile285Thr	missense_variant	Exon 6 of 9	1	NM_022034.6	ENSP00000376540.1	Q86UP6-1
ENSG00000286088	ENST00000368904.6 link	n.*15T>C		non_coding_transcript_exon_variant	Exon 7 of 10	1		ENSP00000357900.2	A0A499FIG0
ENSG00000286088	ENST00000368904.6 link	n.*15T>C		3_prime_UTR_variant	Exon 7 of 10	1		ENSP00000357900.2	A0A499FIG0

Frequencies

GnomAD3 genomes

AF:

0.00569

AC:

864

AN:

151828

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.0144

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00868

Gnomad OTH

AF:

0.00529

GnomAD2 exomes

AF:

0.00577

AC:

1372

AN:

237792

AF XY:

0.00587

show subpopulations

Gnomad AFR exome

AF:

0.00155

Gnomad AMR exome

AF:

0.00134

Gnomad ASJ exome

AF:

0.000843

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0144

Gnomad NFE exome

AF:

0.00853

Gnomad OTH exome

AF:

0.00616

GnomAD4 exome

AF:

0.00761

AC:

11063

AN:

1452978

Hom.:

Cov.:

AF XY:

0.00742

AC XY:

5363

AN XY:

722678

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

32798

American (AMR)

AF:

0.00152

AC:

AN:

42698

Ashkenazi Jewish (ASJ)

AF:

0.00112

AC:

AN:

25790

East Asian (EAS)

AF:

0.00

AC:

AN:

39404

South Asian (SAS)

AF:

0.000782

AC:

AN:

84352

European-Finnish (FIN)

AF:

0.0139

AC:

740

AN:

53206

Middle Eastern (MID)

AF:

0.00105

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.00884

AC:

9805

AN:

1109090

Other (OTH)

AF:

0.00512

AC:

307

AN:

59920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

499

997

1496

1994

2493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

378

756

1134

1512

1890

<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

AF:

0.00568

AC:

863

AN:

151946

Hom.:

Cov.:

AF XY:

0.00598

AC XY:

444

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.00157

AC:

AN:

41420

American (AMR)

AF:

0.00223

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.000416

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0144

AC:

152

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00866

AC:

589

AN:

67988

Other (OTH)

AF:

0.00523

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

123

164

205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00725

Hom.:

Bravo

AF:

0.00462

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.0101

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00942

AC:

ExAC

AF:

0.00590

AC:

716

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.040

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;T

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.69

.;T

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.33

MutationAssessor

Benign

1.5

L;L

PhyloP100

4.3

PROVEAN

Benign

-0.67

N;N

REVEL

Uncertain

0.57

Sift

Benign

0.046

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

1.0

D;D

Vest4

0.28

MVP

0.77

MPC

0.43

ClinPred

0.040

GERP RS

5.2

Varity_R

0.12

gMVP

0.62

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over