chr12-6453644-A-C

Variant names:

• chr12-6453644-A-C
• rs2532500
• NM_018009.5:c.493A>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.493A>C​(p.Thr165Pro) 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. 16/22 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. T165I) 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: 0.618
• Publications: 42 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]

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=0.07494128).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018009.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAPBPL	NM_018009.5	MANE Select	c.493A>C	p.Thr165Pro	missense	Exon 3 of 7	NP_060479.3
	TAPBPL	NM_001351355.2		c.103A>C	p.Thr35Pro	missense	Exon 4 of 8	NP_001338284.1
	TAPBPL	NR_147126.2		n.565A>C		non_coding_transcript_exon	Exon 3 of 8

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAPBPL	ENST00000266556.8	TSL:1 MANE Select	c.493A>C	p.Thr165Pro	missense	Exon 3 of 7	ENSP00000266556.7
	TAPBPL	ENST00000544021.5	TSL:3	c.262A>C	p.Thr88Pro	missense	Exon 2 of 5	ENSP00000445341.1
	TAPBPL	ENST00000539384.5	TSL:5	n.524A>C		non_coding_transcript_exon	Exon 3 of 7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 67

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.35
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.62
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.012
Sift	Benign	0.17	T
Sift4G	Benign	0.21	T
Polyphen		0.0	B
Vest4		0.064
MutPred		0.44		Gain of catalytic residue at K160 (P = 0.0083)
MVP		0.35
MPC		0.23
ClinPred		0.34	T
GERP RS		1.7
Varity_R		0.080
gMVP		0.27
Mutation Taster		=93/7	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: rs2532500; hg19: chr12-6562810;