rs1194076266

Variant names:

• chr10-122836834-T-C
• rs1194076266
• NM_022034.6:c.814A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-122836834-T-C
• chr10-122836834-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022034.6(CUZD1):​c.814A>G​(p.Thr272Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,453,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T272P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CUZD1 NM_022034.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18886387).

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.814A>G	p.Thr272Ala	missense	Exon 5 of 9	NP_071317.2
	CUZD1	NR_037912.2		n.677A>G		non_coding_transcript_exon	Exon 4 of 8
	FAM24B-CUZD1	NR_037915.1		n.1490A>G		non_coding_transcript_exon	Exon 7 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUZD1	ENST00000392790.6	TSL:1 MANE Select	c.814A>G	p.Thr272Ala	missense	Exon 5 of 9	ENSP00000376540.1	Q86UP6-1
	CUZD1	ENST00000368899.5	TSL:1	n.927A>G		non_coding_transcript_exon	Exon 2 of 6
	CUZD1	ENST00000368900.5	TSL:1	n.*355A>G		non_coding_transcript_exon	Exon 4 of 8	ENSP00000357896.2	A0A0A0MRL2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1453878 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723818

African (AFR) AF: 0.00 AC: 0 AN: 33278

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.00 AC: 0 AN: 86054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53292

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000453 AC: 5 AN: 1104952

Other (OTH) AF: 0.00 AC: 0 AN: 60108

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	0.066
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.1
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.11
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.037	D
Polyphen		0.45	B
Vest4		0.20
MutPred		0.33		Loss of glycosylation at T272 (P = 0.1072)
MVP		0.47
MPC		0.081
ClinPred		0.88	D
GERP RS		5.2
Varity_R		0.098
gMVP		0.31
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs1194076266; hg19: chr10-124596350;