chr12-6453081-G-A

Variant names:

• chr12-6453081-G-A
• rs1410789721
• NM_018009.5:c.79G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018009.5(TAPBPL):​c.79G>A​(p.Glu27Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,427,892 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TAPBPL NM_018009.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.90
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2643103).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAPBPL	NM_018009.5	MANE Select	c.79G>A	p.Glu27Lys	missense	Exon 2 of 7	NP_060479.3
	TAPBPL	NM_001351355.2		c.-312G>A		5_prime_UTR	Exon 3 of 8	NP_001338284.1
	TAPBPL	NR_147126.2		n.151G>A		non_coding_transcript_exon	Exon 2 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAPBPL	ENST00000266556.8	TSL:1 MANE Select	c.79G>A	p.Glu27Lys	missense	Exon 2 of 7	ENSP00000266556.7	Q9BX59-1
	TAPBPL	ENST00000853206.1		c.79G>A	p.Glu27Lys	missense	Exon 2 of 8	ENSP00000523265.1
	TAPBPL	ENST00000954553.1		c.79G>A	p.Glu27Lys	missense	Exon 2 of 7	ENSP00000624612.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000508 AC: 1 AN: 196692 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: 0.0000116

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1427892 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 706686

African (AFR) AF: 0.00 AC: 0 AN: 33262

American (AMR) AF: 0.00 AC: 0 AN: 37714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25372

East Asian (EAS) AF: 0.00 AC: 0 AN: 38674

South Asian (SAS) AF: 0.00 AC: 0 AN: 81462

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51166

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5208

European-Non Finnish (NFE) AF: 0.00000274 AC: 3 AN: 1095780

Other (OTH) AF: 0.00 AC: 0 AN: 59254

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0082	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.9
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.093
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.032	D
Polyphen		0.89	P
Vest4		0.44
MutPred		0.35		Gain of catalytic residue at K22 (P = 0)
MVP		0.55
MPC		0.37
ClinPred		0.57	D
GERP RS		3.1
Varity_R		0.20
gMVP		0.54
Mutation Taster		=98/2	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: rs1410789721; hg19: chr12-6562247;