Variant rs2063690 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_017858.3(TIPIN):c.332C>T(p.Ala111Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,613,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. A111G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

TIPIN
NM_017858.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.72

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:

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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, 0.851

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIPIN	NM_017858.3 linkuse as main transcript	c.332C>T	p.Ala111Val	missense_variant	5/8	ENST00000261881.9	NP_060328.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIPIN	ENST00000261881.9 linkuse as main transcript	c.332C>T	p.Ala111Val	missense_variant	5/8	1	NM_017858.3	ENSP00000261881	P1

Frequencies

GnomAD3 genomes

AF:

0.0000987

AC:

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251154

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0000290

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461506

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727044

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.0000447

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000987

AC:

AN:

152036

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.000338

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:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000247

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;.;.;T

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.89

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D;D;D

M_CAP

Benign

0.018

MetaRNN

Pathogenic

0.85

D;D;D;D

MetaSVM

Benign

-0.38

MutationAssessor

Pathogenic

3.3

M;.;.;.

MutationTaster

Benign

1.0e-8

P;P

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-3.3

D;D;D;D

REVEL

Uncertain

0.53

Sift

Uncertain

0.020

D;D;D;D

Sift4G

Uncertain

0.0060

D;.;.;.

Polyphen

1.0

D;.;.;.

Vest4

0.89

MVP

0.67

MPC

0.50

ClinPred

0.83

GERP RS

5.5

Varity_R

0.92

gMVP

0.58

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over