dbSNP rs1254616078: TAPBPL:p.Ala188Thr (chr12-6453713-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018009.5(TAPBPL):c.562G>A(p.Ala188Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

TAPBPL
NM_018009.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.857

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:

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ACMG classification

Classification was made for transcript

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=0.022036672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAPBPL	NM_018009.5 link	c.562G>A	p.Ala188Thr	missense_variant	Exon 3 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.562G>A	p.Ala188Thr	missense_variant	Exon 3 of 7	1	NM_018009.5	ENSP00000266556.7		Q9BX59-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000431

AC:

AN:

231794

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000323

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.96e-7

AC:

AN:

1436238

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711906

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32522

American (AMR)

AF:

0.0000243

AC:

AN:

41180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24826

East Asian (EAS)

AF:

0.00

AC:

AN:

39364

South Asian (SAS)

AF:

0.00

AC:

AN:

84078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52010

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4528

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1098654

Other (OTH)

AF:

0.00

AC:

AN:

59076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 29, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.562G>A (p.A188T) alteration is located in exon 3 (coding exon 3) of the TAPBPL gene. This alteration results from a G to A substitution at nucleotide position 562, causing the alanine (A) at amino acid position 188 to be replaced by a threonine (T). 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

0.071

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.14

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.0090

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.29

.;N

PhyloP100

-0.86

PrimateAI

Benign

0.22

PROVEAN

Benign

0.59

N;N

REVEL

Benign

0.0080

Sift

Benign

0.38

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.0

.;B

Vest4

0.033

MutPred

0.34

.;Gain of catalytic residue at F191 (P = 5e-04);

MVP

0.055

MPC

0.17

ClinPred

0.047

GERP RS

-5.6

Varity_R

0.062

gMVP

0.16

Mutation Taster

=85/15

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

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rs1254616078

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