10-122836186-T-C

Position:

• chr10-122836186-T-C

Variant summary

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

The NM_022034.6(CUZD1):​c.982A>G​(p.Ile328Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CUZD1 NM_022034.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0950

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 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=0.12952742).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUZD1	NM_022034.6	c.982A>G	p.Ile328Val	missense_variant	6/9	ENST00000392790.6
FAM24B-CUZD1	NR_037915.1	n.1658A>G		non_coding_transcript_exon_variant	8/11
CUZD1	NR_037912.2	n.845A>G		non_coding_transcript_exon_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUZD1	ENST00000392790.6	c.982A>G	p.Ile328Val	missense_variant	6/9	1	NM_022034.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1448434 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 720536

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: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2021

The c.982A>G (p.I328V) alteration is located in exon 6 (coding exon 6) of the CUZD1 gene. This alteration results from a A to G substitution at nucleotide position 982, causing the isoleucine (I) at amino acid position 328 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.4
DANN	Benign	0.85
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.55	.;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.95	L;L
MutationTaster	Benign	1.0	D;N;N;N;N;N;N
PROVEAN	Benign	-0.34	N;N
REVEL	Benign	0.10
Sift	Benign	0.44	T;T
Sift4G	Benign	0.82	T;T
Polyphen		0.022	B;B
Vest4		0.099
MutPred		0.56		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.58
MPC		0.056
ClinPred		0.084	T
GERP RS		1.3
Varity_R		0.013
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr10-124595702;