Variant chr21-10541137-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000618007.5(TPTE):c.37G>C(p.Val13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000355 in 1,612,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 6/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 61)

Exomes 𝑓: 0.00037 ( 0 hom. )

Consequence

TPTE
ENST00000618007.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.130

Variant links:

Genes affected

TPTE (HGNC:12023): (transmembrane phosphatase with tensin homology) This gene encodes a PTEN-related tyrosine phosphatase which may play a role in the signal transduction pathways of the endocrine or spermatogenic function of the testis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

TPTE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09008226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TPTE	NM_199261.4 linkuse as main transcript	c.37G>C	p.Val13Leu	missense_variant	5/24	ENST00000618007.5	NP_954870.3
TPTE	NM_199259.4 linkuse as main transcript	c.37G>C	p.Val13Leu	missense_variant	5/23		NP_954868.2
TPTE	NM_199260.4 linkuse as main transcript	c.37G>C	p.Val13Leu	missense_variant	5/22		NP_954869.2
TPTE	NM_001290224.2 linkuse as main transcript	c.-182+13725G>C		intron_variant			NP_001277153.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPTE	ENST00000618007.5 linkuse as main transcript	c.37G>C	p.Val13Leu	missense_variant	5/24	1	NM_199261.4	ENSP00000484403	P2	P56180-1

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152288

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000112

AC:

AN:

251084

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000212

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000367

AC:

536

AN:

1460364

Hom.:

Cov.:

AF XY:

0.000387

AC XY:

281

AN XY:

726552

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

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:

0.0000187

Gnomad4 NFE exome

AF:

0.000470

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000243

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000423

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.37G>C (p.V13L) alteration is located in exon 5 (coding exon 2) of the TPTE gene. This alteration results from a G to C substitution at nucleotide position 37, causing the valine (V) at amino acid position 13 to be replaced by a leucine (L). 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

Benign

0.13

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.5

DANN

Benign

0.91

DEOGEN2

Benign

0.12

.;T;T;.

LIST_S2

Benign

0.34

T;T;T;T

MetaRNN

Benign

0.090

T;T;T;T

Sift4G

Benign

0.17

T;T;D;T

Vest4

0.18

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over