NM_016579.4:c.262_264dupGAG

Variant names:

• chr19-8305034-A-ACTC
• rs150384171
• NM_016579.4:c.262_264dupGAG

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_016579.4(CD320):​c.262_264dupGAG​(p.Glu88dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CD320 NM_016579.4 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.176
• Publications: 16 publications found

Genes affected

CD320 (HGNC:16692): (CD320 molecule) This gene encodes the transcobalamin receptor that is expressed at the cell surface. It mediates the cellular uptake of transcobalamin bound cobalamin (vitamin B12), and is involved in B-cell proliferation and immunoglobulin secretion. Mutations in this gene are associated with methylmalonic aciduria. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2011]

CD320 Gene-Disease associations (from GenCC):

• methylmalonic acidemia due to transcobalamin receptor defect

  Inheritance: Unknown, AR Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, ClinGen, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_016579.4. Strenght limited to Supporting due to length of the change: 1aa.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016579.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD320	NM_016579.4	MANE Select	c.262_264dupGAG	p.Glu88dup	conservative_inframe_insertion	Exon 2 of 5	NP_057663.1
	CD320	NM_001165895.2		c.143-949_143-947dupGAG		intron	N/A	NP_001159367.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD320	ENST00000301458.10	TSL:1 MANE Select	c.262_264dupGAG	p.Glu88dup	conservative_inframe_insertion	Exon 2 of 5	ENSP00000301458.4
	CD320	ENST00000596002.5	TSL:1	n.*665_*667dupGAG		non_coding_transcript_exon	Exon 2 of 5	ENSP00000471773.1
	CD320	ENST00000596002.5	TSL:1	n.*665_*667dupGAG		3_prime_UTR	Exon 2 of 5	ENSP00000471773.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Methylmalonic acidemia due to transcobalamin receptor defect Uncertain:1

Mar 20, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant, c.262_264dup, results in the insertion of 1 amino acid(s) of the CD320 protein (p.Glu88dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CD320-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.18

Splicing

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

Other links and lift over

dbSNP: rs150384171; hg19: chr19-8369918;