chr10-16835111-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001081.4(CUBN):c.10265C>T(p.Thr3422Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0233 in 1,614,004 control chromosomes in the GnomAD database, including 508 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_001081.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CUBN | NM_001081.4 | c.10265C>T | p.Thr3422Ile | missense_variant | 64/67 | ENST00000377833.10 | NP_001072.2 | |
CUBN | XM_011519709.3 | c.6251C>T | p.Thr2084Ile | missense_variant | 38/41 | XP_011518011.1 | ||
CUBN | XM_011519710.3 | c.6227C>T | p.Thr2076Ile | missense_variant | 38/41 | XP_011518012.1 | ||
CUBN | XM_011519711.4 | c.6107C>T | p.Thr2036Ile | missense_variant | 37/40 | XP_011518013.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CUBN | ENST00000377833.10 | c.10265C>T | p.Thr3422Ile | missense_variant | 64/67 | 1 | NM_001081.4 | ENSP00000367064.4 |
Frequencies
GnomAD3 genomes AF: 0.0167 AC: 2539AN: 152100Hom.: 29 Cov.: 33
GnomAD3 exomes AF: 0.0175 AC: 4406AN: 251256Hom.: 63 AF XY: 0.0179 AC XY: 2425AN XY: 135776
GnomAD4 exome AF: 0.0240 AC: 35145AN: 1461786Hom.: 479 Cov.: 32 AF XY: 0.0235 AC XY: 17103AN XY: 727206
GnomAD4 genome AF: 0.0167 AC: 2539AN: 152218Hom.: 29 Cov.: 33 AF XY: 0.0157 AC XY: 1168AN XY: 74418
ClinVar
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 01, 2023 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 26, 2020 | This variant is associated with the following publications: (PMID: 26827111) - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2024 | CUBN: BP4, BS1, BS2 - |
Imerslund-Grasbeck syndrome type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Imerslund-Grasbeck syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at