rs34349100

Variant names:

• chr6-33305284-G-A
• rs34349100
• NM_003190.5:c.573C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_003190.5(TAPBP):​c.573C>T​(p.Ala191Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000392 in 1,588,184 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: TAPBP NM_003190.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0570
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 6-33305284-G-A is Benign according to our data. Variant chr6-33305284-G-A is described in ClinVar as Benign. ClinVar VariationId is 534725.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.057 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAPBP	NM_003190.5	MANE Select	c.573C>T	p.Ala191Ala	synonymous	Exon 4 of 8	NP_003181.3
	TAPBP	NM_172208.3		c.573C>T	p.Ala191Ala	synonymous	Exon 4 of 7	NP_757345.2
	TAPBP	NM_001410875.1		c.573C>T	p.Ala191Ala	synonymous	Exon 4 of 7	NP_001397804.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAPBP	ENST00000434618.7	TSL:1 MANE Select	c.573C>T	p.Ala191Ala	synonymous	Exon 4 of 8	ENSP00000395701.2
	TAPBP	ENST00000426633.6	TSL:1	c.573C>T	p.Ala191Ala	synonymous	Exon 4 of 7	ENSP00000404833.2
	TAPBP	ENST00000489157.6	TSL:1	c.312C>T	p.Ala104Ala	synonymous	Exon 3 of 7	ENSP00000419659.1

Frequencies

GnomAD3 genomes AF: 0.00210 AC: 320 AN: 152136 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00749

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000552 AC: 125 AN: 226654 AF XY: 0.000410

Gnomad AFR exome AF: 0.00779

Gnomad AMR exome AF: 0.0000950

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000971

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000210 AC: 302 AN: 1435930 Hom.: 1 Cov.: 34 AF XY: 0.000198 AC XY: 141 AN XY: 711896

African (AFR) AF: 0.00832 AC: 272 AN: 32684

American (AMR) AF: 0.0000717 AC: 3 AN: 41812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39516

South Asian (SAS) AF: 0.0000486 AC: 4 AN: 82222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5626

European-Non Finnish (NFE) AF: 0.00000728 AC: 8 AN: 1098458

Other (OTH) AF: 0.000253 AC: 15 AN: 59216

GnomAD4 genome AF: 0.00211 AC: 321 AN: 152254 Hom.: 2 Cov.: 32 AF XY: 0.00210 AC XY: 156 AN XY: 74428

African (AFR) AF: 0.00749 AC: 311 AN: 41534

American (AMR) AF: 0.000327 AC: 5 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00151 Hom.: 0

Bravo AF: 0.00264

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	MHC class I deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.7
DANN	Benign	0.50
PhyloP100		0.057
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34349100; hg19: chr6-33273061;