Genetic Variant NM_001348323.3:c.850C>A (chr2-229858949-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001348323.3(TRIP12):c.850C>A(p.Pro284Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

TRIP12
NM_001348323.3 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 9.56

Publications

0 publications found

Variant links:

Genes affected

TRIP12 (HGNC:12306): (thyroid hormone receptor interactor 12) The protein encoded by this gene is an E3 ubiquitin-protein ligase involved in the degradation of the p19ARF/ARF isoform of CDKN2A, a tumor suppressor. The encoded protein also plays a role in the DNA damage response by regulating the stability of USP7, which regulates tumor suppressor p53. [provided by RefSeq, Jan 2017]

TRIP12 Gene-Disease associations (from GenCC):

Clark-Baraitser syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TRIP12 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36766037).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348323.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIP12	NM_001348323.3	MANE Select	c.850C>A	p.Pro284Thr	missense	Exon 4 of 42	NP_001335252.1	A0A6Q8PHK0
TRIP12	NM_001348328.1		c.850C>A	p.Pro284Thr	missense	Exon 4 of 42	NP_001335257.1	A0A6Q8PGG9
TRIP12	NM_001348329.2		c.850C>A	p.Pro284Thr	missense	Exon 4 of 42	NP_001335258.1	A0A6Q8PGG9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIP12	ENST00000675903.1	MANE Select	c.850C>A	p.Pro284Thr	missense	Exon 4 of 42	ENSP00000502713.1	A0A6Q8PHK0
TRIP12	ENST00000389044.8	TSL:1	c.850C>A	p.Pro284Thr	missense	Exon 4 of 42	ENSP00000373696.4	Q14669-3
TRIP12	ENST00000283943.9	TSL:1	c.724C>A	p.Pro242Thr	missense	Exon 3 of 41	ENSP00000283943.4	Q14669-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.055

MetaRNN

Benign

0.37

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.69

PhyloP100

9.6

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.61

REVEL

Benign

0.27

Sift

Uncertain

0.014

Sift4G

Benign

0.25

Polyphen

1.0

Vest4

0.54

MutPred

0.34

Gain of phosphorylation at P242 (P = 4e-04)

MVP

0.24

MPC

0.69

ClinPred

0.55

GERP RS

5.8

PromoterAI

-0.0073

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.24

Mutation Taster

=38/62

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over