chr12-6453708-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018009.5(TAPBPL):​c.557G>A​(p.Arg186Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000464 in 1,594,158 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000044 ( 1 hom. )

Consequence

TAPBPL
NM_018009.5 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.19
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.030219495).
BP6
Variant 12-6453708-G-A is Benign according to our data. Variant chr12-6453708-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3173821.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TAPBPLNM_018009.5 linkuse as main transcriptc.557G>A p.Arg186Gln missense_variant 3/7 ENST00000266556.8 NP_060479.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TAPBPLENST00000266556.8 linkuse as main transcriptc.557G>A p.Arg186Gln missense_variant 3/71 NM_018009.5 ENSP00000266556 P1Q9BX59-1

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152134
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000336
AC:
8
AN:
237946
Hom.:
0
AF XY:
0.0000232
AC XY:
3
AN XY:
129408
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000310
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000555
Gnomad OTH exome
AF:
0.000174
GnomAD4 exome
AF:
0.0000437
AC:
63
AN:
1442024
Hom.:
1
Cov.:
47
AF XY:
0.0000433
AC XY:
31
AN XY:
715354
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000713
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000507
Gnomad4 SAS exome
AF:
0.0000118
Gnomad4 FIN exome
AF:
0.0000572
Gnomad4 NFE exome
AF:
0.0000463
Gnomad4 OTH exome
AF:
0.0000505
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152134
Hom.:
0
Cov.:
33
AF XY:
0.0000942
AC XY:
7
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000108
Hom.:
0
Bravo
AF:
0.000117
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsDec 16, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
0.047
DANN
Benign
0.88
DEOGEN2
Benign
0.0046
T;T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.030
N
LIST_S2
Benign
0.73
T;T
M_CAP
Benign
0.0039
T
MetaRNN
Benign
0.030
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
.;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.17
T
PROVEAN
Benign
-0.96
N;N
REVEL
Benign
0.016
Sift
Benign
0.35
T;T
Sift4G
Benign
0.42
T;T
Polyphen
0.0060
.;B
Vest4
0.021
MutPred
0.46
.;Gain of catalytic residue at F191 (P = 0.0071);
MVP
0.21
MPC
0.21
ClinPred
0.027
T
GERP RS
-9.1
Varity_R
0.099
gMVP
0.21

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs758936057; hg19: chr12-6562874; COSMIC: COSV56946763; COSMIC: COSV56946763; API