Variant 21-10552695-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_199261.4(TPTE):c.212C>G(p.Ala71Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.00016 ( 0 hom., cov: 60)

Exomes 𝑓: 0.00017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TPTE
NM_199261.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.545

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08378732).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TPTE	NM_199261.4 linkuse as main transcript	c.212C>G	p.Ala71Gly	missense_variant	8/24	ENST00000618007.5	NP_954870.3
TPTE	NM_199259.4 linkuse as main transcript	c.158C>G	p.Ala53Gly	missense_variant	7/23		NP_954868.2
TPTE	NM_001290224.2 linkuse as main transcript	c.-181-6799C>G		intron_variant			NP_001277153.2
TPTE	NM_199260.4 linkuse as main transcript	c.120-6799C>G		intron_variant			NP_954869.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPTE	ENST00000618007.5 linkuse as main transcript	c.212C>G	p.Ala71Gly	missense_variant	8/24	1	NM_199261.4	ENSP00000484403	P2	P56180-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152288

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000916

AC:

AN:

250988

Hom.:

AF XY:

0.0000884

AC XY:

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000167

AC:

244

AN:

1461036

Hom.:

Cov.:

AF XY:

0.000166

AC XY:

121

AN XY:

726834

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000209

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000164

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000271

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 13, 2021

The c.212C>G (p.A71G) alteration is located in exon 8 (coding exon 5) of the TPTE gene. This alteration results from a C to G substitution at nucleotide position 212, causing the alanine (A) at amino acid position 71 to be replaced by a glycine (G). 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

0.098

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.4

DANN

Benign

0.44

DEOGEN2

Benign

0.097

.;T;T

LIST_S2

Benign

0.52

T;T;T

MetaRNN

Benign

0.084

T;T;T

Sift4G

Benign

0.62

T;T;T

Vest4

0.22

gMVP

0.60

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