22-30612913-CCT-AGA

Variant names:

• chr22-30612913-CCT-AGA
• NM_000355.4:c.298_300delCCTinsAGA
• TCN2 p.Pro100Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000355.4(TCN2):​c.298_300delCCTinsAGA​(p.Pro100Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P100L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCN2 NM_000355.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 0 publications found

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]

TCN2 Gene-Disease associations (from GenCC):

• transcobalamin II deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, ClinGen, Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000355.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCN2	NM_000355.4	MANE Select	c.298_300delCCTinsAGA	p.Pro100Arg	missense	N/A	NP_000346.2
	TCN2	NM_001184726.2		c.298_300delCCTinsAGA	p.Pro100Arg	missense	N/A	NP_001171655.1	P20062-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCN2	ENST00000215838.8	TSL:1 MANE Select	c.298_300delCCTinsAGA	p.Pro100Arg	missense	N/A	ENSP00000215838.3	P20062-1
	TCN2	ENST00000407817.3	TSL:1	c.298_300delCCTinsAGA	p.Pro100Arg	missense	N/A	ENSP00000384914.3	P20062-2
	TCN2	ENST00000947107.1		c.298_300delCCTinsAGA	p.Pro100Arg	missense	N/A	ENSP00000617166.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-31008900;