Variant chr10-122834857-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022034.6(CUZD1):c.1231G>C(p.Glu411Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CUZD1
NM_022034.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.726

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.121943474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUZD1	NM_022034.6 linkuse as main transcript	c.1231G>C	p.Glu411Gln	missense_variant	7/9	ENST00000392790.6	NP_071317.2	Q86UP6-1
CUZD1	NR_037912.2 linkuse as main transcript	n.1094G>C		non_coding_transcript_exon_variant	6/8
FAM24B-CUZD1	NR_037915.1 linkuse as main transcript	n.1907G>C		non_coding_transcript_exon_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CUZD1	ENST00000392790.6 linkuse as main transcript	c.1231G>C	p.Glu411Gln	missense_variant	7/9	1	NM_022034.6	ENSP00000376540.1	Q86UP6-1
ENSG00000286088	ENST00000368904.6 linkuse as main transcript	n.*392G>C		non_coding_transcript_exon_variant	8/10	1		ENSP00000357900.2	A0A499FIG0
ENSG00000286088	ENST00000368904.6 linkuse as main transcript	n.*392G>C		3_prime_UTR_variant	8/10	1		ENSP00000357900.2	A0A499FIG0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461454

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Aug 02, 2023

The c.1231G>C (p.E411Q) alteration is located in exon 7 (coding exon 7) of the CUZD1 gene. This alteration results from a G to C substitution at nucleotide position 1231, causing the glutamic acid (E) at amino acid position 411 to be replaced by a glutamine (Q). 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

0.090

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.8

DANN

Benign

0.86

DEOGEN2

Benign

0.14

T;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.63

.;T

M_CAP

Benign

0.081

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.7

L;L

PROVEAN

Benign

-0.87

N;N

REVEL

Benign

0.063

Sift

Benign

0.22

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.27

B;B

Vest4

0.080

MutPred

0.41

Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);

MVP

0.66

MPC

0.068

ClinPred

0.14

GERP RS

0.73

Varity_R

0.065

gMVP

0.30

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over