6-33305294-G-C

Variant names:

• chr6-33305294-G-C
• NM_003190.5:c.563C>G
• TAPBP p.Thr188Ser

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003190.5(TAPBP):​c.563C>G​(p.Thr188Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T188I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAPBP NM_003190.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218
• 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: Orphanet, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• MHC class I deficiency 1

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047564775).

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.563C>G	p.Thr188Ser	missense	Exon 4 of 8	NP_003181.3
	TAPBP	NM_172208.3		c.563C>G	p.Thr188Ser	missense	Exon 4 of 7	NP_757345.2	A0A0A0MSV9
	TAPBP	NM_001410875.1		c.563C>G	p.Thr188Ser	missense	Exon 4 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.563C>G	p.Thr188Ser	missense	Exon 4 of 8	ENSP00000395701.2	O15533-1
	TAPBP	ENST00000426633.6	TSL:1	c.563C>G	p.Thr188Ser	missense	Exon 4 of 7	ENSP00000404833.2	O15533-3
	TAPBP	ENST00000489157.6	TSL:1	c.302C>G	p.Thr101Ser	missense	Exon 3 of 7	ENSP00000419659.1	O15533-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	2.6
DANN	Benign	0.53
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.97	T
PhyloP100		0.22
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.010
Sift	Benign	0.59	T
Sift4G	Benign	0.13	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.12
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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: chr6-33273071;