chr12-6452303-G-C

Variant names:

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

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>C​(p.Ala19Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A19T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAPBPL NM_018009.5 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.13149017).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAPBPL	NM_018009.5	c.55G>C	p.Ala19Pro	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>C	p.Ala19Pro	missense_variant	Exon 1 of 7	1	NM_018009.5	ENSP00000266556.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	17
DANN	Benign	0.69
DEOGEN2	Benign	0.0065	T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.42	T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	2.0	.;M
PhyloP100		1.6
PrimateAI	Benign	0.36	T
PROVEAN	Benign	1.9	N;N
REVEL	Benign	0.087
Sift	Benign	0.050	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.27	.;B
Vest4		0.37
MutPred		0.22		Gain of catalytic residue at K22 (P = 5e-04);Gain of catalytic residue at K22 (P = 5e-04);
MVP		0.62
MPC		0.60
ClinPred		0.44	T
GERP RS		2.8
PromoterAI		-0.014	Neutral
Varity_R		0.37
gMVP		0.44
Mutation Taster		=90/10	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;