22-30615687-T-C
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000355.4(TCN2):āc.840T>Cā(p.Asp280=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,614,230 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.0074 ( 15 hom., cov: 33)
Exomes š: 0.00098 ( 15 hom. )
Consequence
TCN2
NM_000355.4 synonymous
NM_000355.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.26
Genes affected
TCN2 (HGNC:11653): (transcobalamin 2) This gene encodes a member of the vitamin B12-binding protein family. This family of proteins, alternatively referred to as R binders, is expressed in various tissues and secretions. This plasma protein binds cobalamin and mediates the transport of cobalamin into cells. This protein and other mammalian cobalamin-binding proteins, such as transcobalamin I and gastric intrisic factor, may have evolved by duplication of a common ancestral gene. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
Variant 22-30615687-T-C is Benign according to our data. Variant chr22-30615687-T-C is described in ClinVar as [Benign]. Clinvar id is 341203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-30615687-T-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-4.26 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00737 (1123/152340) while in subpopulation AFR AF= 0.0248 (1032/41564). AF 95% confidence interval is 0.0236. There are 15 homozygotes in gnomad4. There are 520 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 15 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TCN2 | NM_000355.4 | c.840T>C | p.Asp280= | synonymous_variant | 6/9 | ENST00000215838.8 | NP_000346.2 | |
TCN2 | NM_001184726.2 | c.759T>C | p.Asp253= | synonymous_variant | 6/9 | NP_001171655.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TCN2 | ENST00000215838.8 | c.840T>C | p.Asp280= | synonymous_variant | 6/9 | 1 | NM_000355.4 | ENSP00000215838 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00738 AC: 1123AN: 152222Hom.: 15 Cov.: 33
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GnomAD3 exomes AF: 0.00227 AC: 572AN: 251446Hom.: 9 AF XY: 0.00168 AC XY: 228AN XY: 135896
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GnomAD4 exome AF: 0.000976 AC: 1427AN: 1461890Hom.: 15 Cov.: 35 AF XY: 0.000846 AC XY: 615AN XY: 727246
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GnomAD4 genome AF: 0.00737 AC: 1123AN: 152340Hom.: 15 Cov.: 33 AF XY: 0.00698 AC XY: 520AN XY: 74492
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Transcobalamin II deficiency Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at