chr13-19426462-G-A

Variant names:

• chr13-19426462-G-A
• NM_001395978.1:c.1358C>T

Variant summary

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

The NM_001395978.1(TPTE2):​c.1358C>T​(p.Pro453Leu) 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. 17/22 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)
• Consequence: TPTE2 NM_001395978.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.101
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21562985).

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.1358C>T	p.Pro453Leu	missense	Exon 21 of 23	NP_001382907.1	Q6XPS3-1
	TPTE2	NM_199254.3		c.1358C>T	p.Pro453Leu	missense	Exon 19 of 21	NP_954863.2	Q6XPS3-1
	TPTE2	NM_130785.4		c.1127C>T	p.Pro376Leu	missense	Exon 16 of 18	NP_570141.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPTE2	ENST00000697147.1	MANE Select	c.1358C>T	p.Pro453Leu	missense	Exon 21 of 23	ENSP00000513136.1	Q6XPS3-1
	TPTE2	ENST00000390680.2	TSL:1	c.1127C>T	p.Pro376Leu	missense	Exon 16 of 18	ENSP00000375098.2	Q6XPS3-3
	TPTE2	ENST00000696858.2		c.1358C>T	p.Pro453Leu	missense	Exon 20 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	0.070
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	0.27
DANN	Benign	0.37
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.10
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.24
Sift	Benign	0.22	T
Sift4G	Benign	0.28	T
Polyphen		0.0010	B
Vest4		0.092
MutPred		0.54		Gain of catalytic residue at G451 (P = 0.0013)
MVP		0.22
MPC		0.27
ClinPred		0.035	T
GERP RS		-2.6
Varity_R		0.029
gMVP		0.40
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr13-20000602; COSMIC: COSV105045048;