Genetic Variant TIPIN:p.Thr233Ala (chr15-66337167-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The NM_017858.3(TIPIN):c.697A>G(p.Thr233Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T233P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TIPIN
NM_017858.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.611

Publications

0 publications found

Variant links:

Genes affected

TIPIN (HGNC:30750): (TIMELESS interacting protein) The protein encoded by this gene is part of the replisome complex, a group of proteins that support DNA replication. It binds TIM, which is involved in circadian rhythm regulation, and aids in protecting cells against DNA damage and stress. Two pseudogenes and two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

TIPIN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM1

In a modified_residue Phosphothreonine (size 0) in uniprot entity TIPIN_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05942121).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017858.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TIPIN	NM_017858.3	MANE Select	c.697A>G	p.Thr233Ala	missense	Exon 8 of 8	NP_060328.3	Q9BVW5
TIPIN	NM_001398281.1		c.697A>G	p.Thr233Ala	missense	Exon 8 of 8	NP_001385210.1	Q9BVW5
TIPIN	NM_001398282.1		c.697A>G	p.Thr233Ala	missense	Exon 8 of 8	NP_001385211.1	Q9BVW5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TIPIN	ENST00000261881.9	TSL:1 MANE Select	c.697A>G	p.Thr233Ala	missense	Exon 8 of 8	ENSP00000261881.4	Q9BVW5
TIPIN	ENST00000851323.1		c.697A>G	p.Thr233Ala	missense	Exon 8 of 8	ENSP00000521382.1
TIPIN	ENST00000851324.1		c.697A>G	p.Thr233Ala	missense	Exon 7 of 7	ENSP00000521383.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461166

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726856

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

86218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53132

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111770

Other (OTH)

AF:

0.00

AC:

AN:

60370

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

7.9

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.0042

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.46

M_CAP

Benign

0.0038

MetaRNN

Benign

0.059

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.5

PhyloP100

0.61

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.79

REVEL

Benign

0.027

Sift

Benign

0.067

Sift4G

Benign

0.74

Polyphen

0.0020

Vest4

0.077

MutPred

0.092

Loss of glycosylation at T233 (P = 0.0357)

MVP

0.055

MPC

0.095

ClinPred

0.071

GERP RS

-0.52

Varity_R

0.028

gMVP

0.097

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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