10-122836231-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_022034.6(CUZD1):​c.937T>A​(p.Ser313Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,612,708 control chromosomes in the GnomAD database, including 3 homozygotes. 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: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 3 hom. )

Consequence

CUZD1
NM_022034.6 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.127
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0134138465).
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CUZD1NM_022034.6 linkuse as main transcriptc.937T>A p.Ser313Thr missense_variant 6/9 ENST00000392790.6 NP_071317.2 Q86UP6-1
CUZD1NR_037912.2 linkuse as main transcriptn.800T>A non_coding_transcript_exon_variant 5/8
FAM24B-CUZD1NR_037915.1 linkuse as main transcriptn.1613T>A non_coding_transcript_exon_variant 8/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CUZD1ENST00000392790.6 linkuse as main transcriptc.937T>A p.Ser313Thr missense_variant 6/91 NM_022034.6 ENSP00000376540.1 Q86UP6-1
ENSG00000286088ENST00000368904.6 linkuse as main transcriptn.*98T>A non_coding_transcript_exon_variant 7/101 ENSP00000357900.2 A0A499FIG0
ENSG00000286088ENST00000368904.6 linkuse as main transcriptn.*98T>A 3_prime_UTR_variant 7/101 ENSP00000357900.2 A0A499FIG0

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152144
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00103
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000220
AC:
55
AN:
249870
Hom.:
0
AF XY:
0.000303
AC XY:
41
AN XY:
135116
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000877
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00129
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000115
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000139
AC:
203
AN:
1460446
Hom.:
3
Cov.:
31
AF XY:
0.000184
AC XY:
134
AN XY:
726506
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000900
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00134
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000702
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000919
AC:
14
AN:
152262
Hom.:
0
Cov.:
32
AF XY:
0.000134
AC XY:
10
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000450
Hom.:
0
Bravo
AF:
0.0000491
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000255
AC:
31
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.0000594

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 submitterclinical testingAmbry GeneticsJul 13, 2021The c.937T>A (p.S313T) alteration is located in exon 6 (coding exon 6) of the CUZD1 gene. This alteration results from a T to A substitution at nucleotide position 937, causing the serine (S) at amino acid position 313 to be replaced by a threonine (T). 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
0.085
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
5.6
DANN
Benign
0.38
DEOGEN2
Benign
0.12
T;T
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.78
FATHMM_MKL
Benign
0.010
N
LIST_S2
Benign
0.45
.;T
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.013
T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
2.0
M;M
PROVEAN
Benign
1.3
N;N
REVEL
Benign
0.13
Sift
Benign
0.58
T;T
Sift4G
Benign
0.36
T;T
Polyphen
0.17
B;B
Vest4
0.066
MVP
0.63
MPC
0.081
ClinPred
0.024
T
GERP RS
2.6
Varity_R
0.033
gMVP
0.67

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

LitVar

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

Other links and lift over

dbSNP: rs367680605; hg19: chr10-124595747; API