Genetic Variant NM_015508.5:c.406C>T (chr3-156678103-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015508.5(TIPARP):c.406C>T(p.Pro136Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,614,110 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P136A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 2 hom. )

Consequence

TIPARP
NM_015508.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.91

Publications

0 publications found

Variant links:

Genes affected

TIPARP (HGNC:23696): (TCDD inducible poly(ADP-ribose) polymerase) This gene encodes a member of the poly(ADP-ribose) polymerase superfamily. Studies of the mouse ortholog have shown that the encoded protein catalyzes histone poly(ADP-ribosyl)ation and may be involved in T-cell function. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

TIPARP links:

TIPARP-AS1 (HGNC:41028): (TIPARP antisense RNA 1)

TIPARP-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024512798).

BS2

High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015508.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TIPARP	NM_015508.5	MANE Select	c.406C>T	p.Pro136Ser	missense	Exon 2 of 6	NP_056323.2
TIPARP	NM_001184717.1		c.406C>T	p.Pro136Ser	missense	Exon 2 of 6	NP_001171646.1	Q7Z3E1
TIPARP	NM_001184718.2		c.406C>T	p.Pro136Ser	missense	Exon 2 of 6	NP_001171647.1	Q7Z3E1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TIPARP	ENST00000295924.12	TSL:1 MANE Select	c.406C>T	p.Pro136Ser	missense	Exon 2 of 6	ENSP00000295924.7	Q7Z3E1
TIPARP	ENST00000461166.5	TSL:1	c.406C>T	p.Pro136Ser	missense	Exon 2 of 6	ENSP00000420612.1	Q7Z3E1
TIPARP	ENST00000542783.5	TSL:1	c.406C>T	p.Pro136Ser	missense	Exon 2 of 6	ENSP00000438345.1	Q7Z3E1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000915

AC:

AN:

251350

AF XY:

0.000118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000465

AC:

AN:

1461796

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000754

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112010

Other (OTH)

AF:

0.0000331

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41546

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00103

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.000107

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.034

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.80

M_CAP

Benign

0.0040

MetaRNN

Benign

0.025

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

2.9

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.59

REVEL

Benign

0.034

Sift

Benign

0.042

Sift4G

Benign

0.21

Polyphen

0.028

Vest4

0.12

MutPred

0.32

Gain of sheet (P = 0.0125)

MVP

0.15

MPC

0.28

ClinPred

0.082

GERP RS

4.2

Varity_R

0.13

gMVP

0.33

Mutation Taster

=100/0

polymorphism

(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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over