13-19432533-A-G

Position:

• chr13-19432533-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001395978.1(TPTE2):​c.1162T>C​(p.Trp388Arg) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.000015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TPTE2 NM_001395978.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0540

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06552392).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPTE2	NM_001395978.1	c.1162T>C	p.Trp388Arg	missense_variant	19/23	ENST00000697147.1	NP_001382907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPTE2	ENST00000697147.1	c.1162T>C	p.Trp388Arg	missense_variant	19/23		NM_001395978.1	ENSP00000513136	P2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000151 AC: 22 AN: 1455624 Hom.: 0 Cov.: 30 AF XY: 0.0000152 AC XY: 11 AN XY: 724136

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000198

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.1162T>C (p.W388R) alteration is located in exon 17 (coding exon 16) of the TPTE2 gene. This alteration results from a T to C substitution at nucleotide position 1162, causing the tryptophan (W) at amino acid position 388 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	1.3
DANN	Benign	0.33
DEOGEN2	Uncertain	0.47	.;T;.;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0084	N
LIST_S2	Benign	0.76	T;T;T;T;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.066	T;T;T;T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.1	.;L;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-5.0	D;D;D;D;D
REVEL	Benign	0.20
Sift	Benign	0.62	T;T;T;T;T
Sift4G	Benign	0.56	T;T;T;T;T
Polyphen		0.0040, 0.0010	.;B;B;.;B
Vest4		0.15
MutPred		0.49		.;Gain of catalytic residue at P391 (P = 0);.;.;.;
MVP		0.28
MPC		0.47
ClinPred		0.045	T
GERP RS		-3.8
Varity_R		0.096
gMVP		0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs764470955; hg19: chr13-20006673;