rs36212072

Variant names:

• chr10-122836314-A-G
• rs36212072
• NM_022034.6:c.854T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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)

ENSG00000286088 (HGNC:):

ACMG classification

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUZD1	NM_022034.6	MANE Select	c.854T>C	p.Ile285Thr	missense	Exon 6 of 9	NP_071317.2
	CUZD1	NR_037912.2		n.717T>C		non_coding_transcript_exon	Exon 5 of 8
	FAM24B-CUZD1	NR_037915.1		n.1530T>C		non_coding_transcript_exon	Exon 8 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUZD1	ENST00000392790.6	TSL:1 MANE Select	c.854T>C	p.Ile285Thr	missense	Exon 6 of 9	ENSP00000376540.1	Q86UP6-1
	CUZD1	ENST00000368899.5	TSL:1	n.967T>C		non_coding_transcript_exon	Exon 3 of 6
	CUZD1	ENST00000368900.5	TSL:1	n.*395T>C		non_coding_transcript_exon	Exon 5 of 8	ENSP00000357896.2	A0A0A0MRL2

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

GnomAD2 exomes AF: 0.00577 AC: 1372 AN: 237792 AF XY: 0.00587

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

African (AFR) AF: 0.00137 AC: 45 AN: 32798

American (AMR) AF: 0.00152 AC: 65 AN: 42698

Ashkenazi Jewish (ASJ) AF: 0.00112 AC: 29 AN: 25790

East Asian (EAS) AF: 0.00 AC: 0 AN: 39404

South Asian (SAS) AF: 0.000782 AC: 66 AN: 84352

European-Finnish (FIN) AF: 0.0139 AC: 740 AN: 53206

Middle Eastern (MID) AF: 0.00105 AC: 6 AN: 5720

European-Non Finnish (NFE) AF: 0.00884 AC: 9805 AN: 1109090

Other (OTH) AF: 0.00512 AC: 307 AN: 59920

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

African (AFR) AF: 0.00157 AC: 65 AN: 41420

American (AMR) AF: 0.00223 AC: 34 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4810

European-Finnish (FIN) AF: 0.0144 AC: 152 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00866 AC: 589 AN: 67988

Other (OTH) AF: 0.00523 AC: 11 AN: 2102

Alfa AF: 0.00725 Hom.: 7

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 v4.9

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
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
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.5	L
PhyloP100		4.3
PROVEAN	Benign	-0.67	N
REVEL	Uncertain	0.57
Sift	Benign	0.046	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	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
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs36212072; hg19: chr10-124595830;