dbSNP rs761880008: TAPBPL:p.Lys305Glu (chr12-6458653-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018009.5(TAPBPL):c.913A>G(p.Lys305Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TAPBPL
NM_018009.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42

Publications

0 publications found

Variant links:

Genes affected

TAPBPL (HGNC:30683): (TAP binding protein like) Tapasin, or TAPBP (MIM 601962), is a member of the variable-constant Ig superfamily that links major histocompatibility complex (MHC) class I molecules to the transporter associated with antigen processing (TAP; see MIM 170260) in the endoplasmic reticulum (ER). The TAPBP gene is located near the MHC complex on chromosome 6p21.3. TAPBPL is a member of the Ig superfamily that is localized on chromosome 12p13.3, a region somewhat paralogous to the MHC.[supplied by OMIM, Mar 2008]

TAPBPL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20001718).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAPBPL	NM_018009.5 link	c.913A>G	p.Lys305Glu	missense_variant	Exon 5 of 7	ENST00000266556.8	NP_060479.3	Q9BX59-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAPBPL	ENST00000266556.8 link	c.913A>G	p.Lys305Glu	missense_variant	Exon 5 of 7	1	NM_018009.5	ENSP00000266556.7		Q9BX59-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250482

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460738

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726416

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111032

Other (OTH)

AF:

0.00

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.913A>G (p.K305E) alteration is located in exon 5 (coding exon 5) of the TAPBPL gene. This alteration results from a A to G substitution at nucleotide position 913, causing the lysine (K) at amino acid position 305 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0094

Eigen

Benign

-0.031

Eigen_PC

Benign

0.075

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.76

M_CAP

Benign

0.013

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

2.4

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.8

REVEL

Benign

0.070

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.018

Polyphen

0.22

Vest4

0.39

MutPred

0.44

Gain of catalytic residue at R307 (P = 0.0155);

MVP

0.44

MPC

0.27

ClinPred

0.56

GERP RS

5.0

Varity_R

0.71

gMVP

0.34

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs761880008

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over