13-19423163-G-C

Variant names:

• chr13-19423163-G-C
• NM_001395978.1:c.1468C>G

Variant summary

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

The NM_001395978.1(TPTE2):​c.1468C>G​(p.Leu490Val) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TPTE2 NM_001395978.1 missense, splice_region
• Scores: Splicing: ADA: 0.0006896
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17
• Publications: 0 publications found

Genes affected

TPTE2 (HGNC:17299): (transmembrane phosphoinositide 3-phosphatase and tensin homolog 2) TPIP is a member of a large class of membrane-associated phosphatases with substrate specificity for the 3-position phosphate of inositol phospholipids.[supplied by OMIM, Jul 2002]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395978.1. 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
	TPTE2	NM_001395978.1	MANE Select	c.1468C>G	p.Leu490Val	missense splice_region	Exon 23 of 23	NP_001382907.1	Q6XPS3-1
	TPTE2	NM_199254.3		c.1468C>G	p.Leu490Val	missense splice_region	Exon 21 of 21	NP_954863.2	Q6XPS3-1
	TPTE2	NM_130785.4		c.1237C>G	p.Leu413Val	missense splice_region	Exon 18 of 18	NP_570141.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPTE2	ENST00000697147.1	MANE Select	c.1468C>G	p.Leu490Val	missense splice_region	Exon 23 of 23	ENSP00000513136.1	Q6XPS3-1
	TPTE2	ENST00000390680.2	TSL:1	c.1237C>G	p.Leu413Val	missense splice_region	Exon 18 of 18	ENSP00000375098.2	Q6XPS3-3
	TPTE2	ENST00000696858.2		c.1468C>G	p.Leu490Val	missense splice_region	Exon 22 of 22	ENSP00000512931.1	Q6XPS3-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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	0.20
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	23
DANN	Benign	0.88
DEOGEN2	Uncertain	0.65	D
Eigen	Benign	-0.046
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Uncertain	0.20	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.2
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.49
Sift	Benign	0.10	T
Sift4G	Benign	0.087	T
Polyphen		0.65	P
Vest4		0.55
MutPred		0.68		Gain of catalytic residue at L492 (P = 2e-04)
MVP		0.81
MPC		0.70
ClinPred		0.66	D
GERP RS		2.1
Varity_R		0.21
gMVP		0.55
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00069
dbscSNV1_RF	Benign	0.042
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

Other links and lift over

hg19: chr13-19997303;