Variant 1-168191489-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_152902.5(TIPRL):c.505A>C(p.Ser169Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000141 in 1,348,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TIPRL
NM_152902.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.58

Variant links:

Genes affected

TIPRL (HGNC:30231): (TOR signaling pathway regulator) TIPRL is an inhibitory regulator of protein phosphatase-2A (PP2A) (see PPP2CA; MIM 176915), PP4 (see PPP4C; MIM 602035), and PP6 (see PPP6C; MIM 612725) (McConnell et al., 2007 [PubMed 17384681]).[supplied by OMIM, Nov 2010]

TIPRL links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.89

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIPRL	NM_152902.5 linkuse as main transcript	c.505A>C	p.Ser169Arg	missense_variant	4/7	ENST00000367833.7	NP_690866.1	O75663-1
TIPRL	NM_001031800.3 linkuse as main transcript	c.505A>C	p.Ser169Arg	missense_variant	4/5		NP_001026970.1	O75663-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIPRL	ENST00000367833.7 linkuse as main transcript	c.505A>C	p.Ser169Arg	missense_variant	4/7	1	NM_152902.5	ENSP00000356807.2		O75663-1
TIPRL	ENST00000367830.3 linkuse as main transcript	c.505A>C	p.Ser169Arg	missense_variant	4/5	1		ENSP00000356804.3		O75663-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000141

AC:

AN:

1348220

Hom.:

Cov.:

AF XY:

0.0000150

AC XY:

AN XY:

667464

show subpopulations

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:

0.0000178

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Apr 08, 2022

The c.505A>C (p.S169R) alteration is located in exon 4 (coding exon 4) of the TIPRL gene. This alteration results from a A to C substitution at nucleotide position 505, causing the serine (S) at amino acid position 169 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

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.35

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.035

MetaRNN

Pathogenic

0.89

D;D

MetaSVM

Uncertain

-0.070

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.3

D;D

REVEL

Pathogenic

0.91

Sift

Benign

0.046

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

D;B

Vest4

0.89

MutPred

0.78

Gain of MoRF binding (P = 0.0161);Gain of MoRF binding (P = 0.0161);

MVP

0.32

MPC

0.82

ClinPred

0.98

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.79

gMVP

0.89

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

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