NM_003190.5:c.470-3606T>A

Variant names:

• chr6-33308993-A-T
• rs9277972
• NM_003190.5:c.470-3606T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003190.5(TAPBP):​c.470-3606T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,140 control chromosomes in the GnomAD database, including 1,801 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1801 hom., cov: 31)
• Consequence: TAPBP NM_003190.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291
• Publications: 16 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAPBP	NM_003190.5	c.470-3606T>A		intron_variant	Intron 3 of 7	ENST00000434618.7	NP_003181.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAPBP	ENST00000434618.7	c.470-3606T>A		intron_variant	Intron 3 of 7	1	NM_003190.5	ENSP00000395701.2

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21460 AN: 152022 Hom.: 1797 Cov.: 31

Gnomad AFR AF: 0.0543

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.0944

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.141 AC: 21469 AN: 152140 Hom.: 1801 Cov.: 31 AF XY: 0.141 AC XY: 10527 AN XY: 74400

African (AFR) AF: 0.0542 AC: 2249 AN: 41520

American (AMR) AF: 0.136 AC: 2073 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 865 AN: 3468

East Asian (EAS) AF: 0.0944 AC: 490 AN: 5190

South Asian (SAS) AF: 0.279 AC: 1344 AN: 4824

European-Finnish (FIN) AF: 0.143 AC: 1517 AN: 10574

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.182 AC: 12357 AN: 67992

Other (OTH) AF: 0.169 AC: 356 AN: 2110

Alfa AF: 0.0539 Hom.: 66

Bravo AF: 0.135

Asia WGS AF: 0.203 AC: 704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.71
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs9277972; hg19: chr6-33276770;