rs36212072

Positions:

• chr10-122836314-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.29

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]

FAM24B-CUZD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010733813).
• BS2: High Homozygotes in GnomAdExome4 at 45 AR gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUZD1	ENST00000392790.6	c.854T>C	p.Ile285Thr	missense_variant	6/9	1	NM_022034.6	ENSP00000376540	P1

Frequencies

GnomAD3 genomes AF: 0.00569 AC: 864 AN: 151828 Hom.: 1 Cov.: 32

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

GnomAD3 exomes AF: 0.00577 AC: 1372 AN: 237792 Hom.: 4 AF XY: 0.00587 AC XY: 756 AN XY: 128874

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 SAS exome AF: 0.000863

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.: 45 Cov.: 31 AF XY: 0.00742 AC XY: 5363 AN XY: 722678

Gnomad4 AFR exome AF: 0.00137

Gnomad4 AMR exome AF: 0.00152

Gnomad4 ASJ exome AF: 0.00112

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000782

Gnomad4 FIN exome AF: 0.0139

Gnomad4 NFE exome AF: 0.00884

Gnomad4 OTH exome AF: 0.00512

GnomAD4 genome AF: 0.00568 AC: 863 AN: 151946 Hom.: 1 Cov.: 32 AF XY: 0.00598 AC XY: 444 AN XY: 74256

Gnomad4 AFR AF: 0.00157

Gnomad4 AMR AF: 0.00223

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.0144

Gnomad4 NFE AF: 0.00866

Gnomad4 OTH AF: 0.00523

Alfa AF: 0.00765 Hom.: 6

Bravo AF: 0.00462

TwinsUK AF: 0.00782 AC: 29

ALSPAC AF: 0.0101 AC: 39

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00942 AC: 81

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	T
BayesDel_noAF	Uncertain	0.040
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.69	.;T
MetaRNN	Benign	0.011	T;T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.5	L;L
MutationTaster	Benign	0.98	D;D;D;D;D;D;D
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	T
GERP RS		5.2
Varity_R		0.12
gMVP		0.62

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

LitVar

Other links and lift over

dbSNP: rs36212072; hg19: chr10-124595830;