13-19432548-T-C

Variant names:

• chr13-19432548-T-C
• rs1167521152
• NM_001395978.1:c.1147A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001395978.1(TPTE2):​c.1147A>G​(p.Lys383Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,452,994 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TPTE2 NM_001395978.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.24

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPTE2	NM_001395978.1	c.1147A>G	p.Lys383Glu	missense_variant	Exon 19 of 23	ENST00000697147.1	NP_001382907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPTE2	ENST00000697147.1	c.1147A>G	p.Lys383Glu	missense_variant	Exon 19 of 23		NM_001395978.1	ENSP00000513136.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452994 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 722970

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: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1147A>G (p.K383E) alteration is located in exon 17 (coding exon 16) of the TPTE2 gene. This alteration results from a A to G substitution at nucleotide position 1147, causing the lysine (K) at amino acid position 383 to be replaced by a glutamic acid (E). 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	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.59	.;D;.;.;.
Eigen	Benign	0.010
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.88	D;D;D;D;.
M_CAP	Benign	0.0089	T
MetaRNN	Uncertain	0.72	D;D;D;D;D
MetaSVM	Uncertain	0.38	D
MutationAssessor	Pathogenic	3.1	.;M;.;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.3	D;D;D;D;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.022	D;D;D;T;D
Sift4G	Benign	0.14	T;T;T;T;T
Polyphen		0.99, 0.89	.;D;P;.;P
Vest4		0.68
MutPred		0.57		.;Gain of catalytic residue at Q381 (P = 0);.;.;.;
MVP		0.77
MPC		0.57
ClinPred		0.95	D
GERP RS		2.6
Varity_R		0.43
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1167521152; hg19: chr13-20006688;