rs759400818

Variant names:

• chr10-122832399-C-G
• NM_022034.6:c.1703G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-122832399-C-G
• chr10-122832399-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022034.6(CUZD1):​c.1703G>C​(p.Ser568Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CUZD1 NM_022034.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800

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]

ENSG00000286088 (HGNC:):

ACMG classification

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=0.09277171).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUZD1	NM_022034.6	c.1703G>C	p.Ser568Thr	missense_variant	Exon 9 of 9	ENST00000392790.6	NP_071317.2
CUZD1	NR_037912.2	n.1566G>C		non_coding_transcript_exon_variant	Exon 8 of 8
FAM24B-CUZD1	NR_037915.1	n.2379G>C		non_coding_transcript_exon_variant	Exon 11 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUZD1	ENST00000392790.6	c.1703G>C	p.Ser568Thr	missense_variant	Exon 9 of 9	1	NM_022034.6	ENSP00000376540.1
ENSG00000286088	ENST00000368904.6	n.*864G>C		non_coding_transcript_exon_variant	Exon 10 of 10	1		ENSP00000357900.2
ENSG00000286088	ENST00000368904.6	n.*864G>C		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000357900.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461828 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727216

Gnomad4 AFR exome AF: 0.00

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: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.8
DANN	Benign	0.81
DEOGEN2	Benign	0.075	T;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.46	.;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.093	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M
PROVEAN	Benign	-0.45	N;N
REVEL	Benign	0.084
Sift	Benign	0.40	T;T
Sift4G	Benign	0.099	T;T
Polyphen		0.18	B;B
Vest4		0.29
MutPred		0.54		Gain of glycosylation at S568 (P = 0.0365);Gain of glycosylation at S568 (P = 0.0365);
MVP		0.33
MPC		0.076
ClinPred		0.15	T
GERP RS		2.2
Varity_R		0.065
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr10-124591915;