TAPBP p.Leu418Leu

Variant names:

• chr6-33304173-A-A
• NM_003190.5:c.

Your query was ambiguous. Multiple possible variants found:

• chr6-33304174--
• chr6-33304176-G-A
• chr6-33304174-C-A
• chr6-33304174-C-G
• chr6-33304174-C-T
• chr6-33304174-CAG-TAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003190.5(TAPBP):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TAPBP NM_003190.5 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202
• Publications: 0 publications found

Genes affected

TAPBP (HGNC:11566): (TAP binding protein) This gene encodes a transmembrane glycoprotein which mediates interaction between newly assembled major histocompatibility complex (MHC) class I molecules and the transporter associated with antigen processing (TAP), which is required for the transport of antigenic peptides across the endoplasmic reticulum membrane. This interaction is essential for optimal peptide loading on the MHC class I molecule. Up to four complexes of MHC class I and this protein may be bound to a single TAP molecule. This protein contains a C-terminal double-lysine motif (KKKAE) known to maintain membrane proteins in the endoplasmic reticulum. This gene lies within the major histocompatibility complex on chromosome 6. Alternative splicing results in three transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

TAPBP Gene-Disease associations (from GenCC):

• MHC class I deficiency

  Inheritance: AR Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Orphanet
• MHC class I deficiency 1

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003190.5. 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
	TAPBP	NM_003190.5	MANE Select	c.		exon_region	Exon 6 of 8	NP_003181.3
	TAPBP	NM_172208.3		c.		exon_region	Exon 6 of 7	NP_757345.2	A0A0A0MSV9
	TAPBP	NM_001410875.1		c.		exon_region	Exon 6 of 7	NP_001397804.1	A0A8V8TQC5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAPBP	ENST00000434618.7	TSL:1 MANE Select	c.		exon_region	Exon 6 of 8	ENSP00000395701.2	O15533-1
	TAPBP	ENST00000426633.6	TSL:1	c.		exon_region	Exon 6 of 7	ENSP00000404833.2	O15533-3
	TAPBP	ENST00000489157.6	TSL:1	c.		exon_region	Exon 5 of 7	ENSP00000419659.1	O15533-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.20

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: chr6-33271950;