rs138516982

chr6-33304194-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003190.5(TAPBP):c.1234G>A(p.Asp412Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000403 in 1,613,762 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 31)
  • Exomes 𝑓: 0.00025 (1 hom.)
• Consequence: TAPBP NM_003190.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.08

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007776201).
• BP6: Variant 6-33304194-C-T is Benign according to our data. Variant chr6-33304194-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 534736.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAPBP	NM_003190.5	c.1234G>A	p.Asp412Asn	missense_variant	6/8	ENST00000434618.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAPBP	ENST00000434618.7	c.1234G>A	p.Asp412Asn	missense_variant	6/8	1	NM_003190.5	P2

Frequencies

GnomAD3 genomes AF: 0.00184 AC: 280 AN: 151878 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00612

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

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: 0.0000294

Gnomad OTH AF: 0.000960

GnomAD3 exomes AF: 0.000542 AC: 136 AN: 251036 Hom.: 0 AF XY: 0.000391 AC XY: 53 AN XY: 135686

Gnomad AFR exome AF: 0.00616

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000253 AC: 370 AN: 1461766 Hom.: 1 Cov.: 32 AF XY: 0.000220 AC XY: 160 AN XY: 727196

Gnomad4 AFR exome AF: 0.00651

Gnomad4 AMR exome AF: 0.000939

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000639

Gnomad4 OTH exome AF: 0.000580

GnomAD4 genome AF: 0.00184 AC: 280 AN: 151996 Hom.: 2 Cov.: 31 AF XY: 0.00188 AC XY: 140 AN XY: 74278

Gnomad4 AFR AF: 0.00610

Gnomad4 AMR AF: 0.00151

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000950

Alfa AF: 0.000314 Hom.: 0

Bravo AF: 0.00219

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00635 AC: 28

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000651 AC: 79

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MHC class I deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 04, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.46
Cadd	Uncertain	24
Dann	Pathogenic	1.0
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.0078	T;T;T;T
MetaSVM	Benign	-0.80	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	.;D;.;.
Vest4		0.69
MVP		0.45
MPC		1.1
ClinPred		0.033	T
GERP RS		5.4
gMVP		0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs138516982; hg19: chr6-33271971;