12-6452303-G-A

Variant names:

• chr12-6452303-G-A
• rs745730271
• NM_018009.5:c.55G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018009.5(TAPBPL):​c.55G>A​(p.Ala19Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000318 in 1,574,614 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: TAPBPL NM_018009.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57
• Publications: 0 publications found

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]

CD27-AS1 (HGNC:43896): (CD27 antisense RNA 1)

ACMG classification

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=0.09157145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAPBPL	NM_018009.5	c.55G>A	p.Ala19Thr	missense_variant	Exon 1 of 7	ENST00000266556.8	NP_060479.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAPBPL	ENST00000266556.8	c.55G>A	p.Ala19Thr	missense_variant	Exon 1 of 7	1	NM_018009.5	ENSP00000266556.7

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 185846 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000281 AC: 4 AN: 1422266 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 703232

African (AFR) AF: 0.00 AC: 0 AN: 33218

American (AMR) AF: 0.00 AC: 0 AN: 36660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25294

East Asian (EAS) AF: 0.00 AC: 0 AN: 38592

South Asian (SAS) AF: 0.00 AC: 0 AN: 80830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50788

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5324

European-Non Finnish (NFE) AF: 0.00000366 AC: 4 AN: 1092524

Other (OTH) AF: 0.00 AC: 0 AN: 59036

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152348 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74508

African (AFR) AF: 0.00 AC: 0 AN: 41578

American (AMR) AF: 0.00 AC: 0 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000258 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 29, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.55G>A (p.A19T) alteration is located in exon 1 (coding exon 1) of the TAPBPL gene. This alteration results from a G to A substitution at nucleotide position 55, causing the alanine (A) at amino acid position 19 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	0.094
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Benign	0.72
DEOGEN2	Benign	0.0062	T;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.45	T;T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.092	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	2.0	.;M
PhyloP100		1.6
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.24	N;N
REVEL	Benign	0.068
Sift	Benign	0.036	D;D
Sift4G	Pathogenic	0.0	D;T
Polyphen		0.048	.;B
Vest4		0.093
MutPred		0.18		Gain of catalytic residue at K22 (P = 0);Gain of catalytic residue at K22 (P = 0);
MVP		0.56
MPC		0.39
ClinPred		0.51	D
GERP RS		2.8
PromoterAI		0.034	Neutral
Varity_R		0.12
gMVP		0.26
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs745730271; hg19: chr12-6561469;