chr10-122834711-C-T

Variant names:

• chr10-122834711-C-T
• rs1327590386
• NM_022034.6:c.1377G>A

Variant summary

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

The NM_022034.6(CUZD1):​c.1377G>A​(p.Lys459Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CUZD1 NM_022034.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUZD1	NM_022034.6	c.1377G>A	p.Lys459Lys	synonymous_variant	Exon 7 of 9	ENST00000392790.6	NP_071317.2
CUZD1	NR_037912.2	n.1240G>A		non_coding_transcript_exon_variant	Exon 6 of 8
FAM24B-CUZD1	NR_037915.1	n.2053G>A		non_coding_transcript_exon_variant	Exon 9 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUZD1	ENST00000392790.6	c.1377G>A	p.Lys459Lys	synonymous_variant	Exon 7 of 9	1	NM_022034.6	ENSP00000376540.1
ENSG00000286088	ENST00000368904.6	n.*538G>A		non_coding_transcript_exon_variant	Exon 8 of 10	1		ENSP00000357900.2
ENSG00000286088	ENST00000368904.6	n.*538G>A		3_prime_UTR_variant	Exon 8 of 10	1		ENSP00000357900.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.33		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1327590386; hg19: chr10-124594227;