19-8305034-ACTC-ACTCCTC

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

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

Sel.	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	Q9NPF0-1
	CD320	NM_001165895.2		c.143-949_143-947dupGAG		intron	N/A	NP_001159367.1	Q9NPF0-2

Ensembl Transcripts

Sel.	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	Q9NPF0-1
	CD320	ENST00000596002.5	TSL:1	n.*665_*667dupGAG		non_coding_transcript_exon	Exon 2 of 5	ENSP00000471773.1	M0R1C4
	CD320	ENST00000596002.5	TSL:1	n.*665_*667dupGAG		3_prime_UTR	Exon 2 of 5	ENSP00000471773.1	M0R1C4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Methylmalonic acidemia due to transcobalamin receptor defect (1)

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;