chr3-156677875-T-A

Position:

• chr3-156677875-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015508.5(TIPARP):​c.178T>A​(p.Leu60Ile) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TIPARP NM_015508.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.53

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.108707964).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIPARP	NM_015508.5	c.178T>A	p.Leu60Ile	missense_variant	2/6	ENST00000295924.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIPARP	ENST00000295924.12	c.178T>A	p.Leu60Ile	missense_variant	2/6	1	NM_015508.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2023

The c.178T>A (p.L60I) alteration is located in exon 2 (coding exon 1) of the TIPARP gene. This alteration results from a T to A substitution at nucleotide position 178, causing the leucine (L) at amino acid position 60 to be replaced by an isoleucine (I). 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	Benign	0.14
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.12	T;T;T;.;.;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.68	.;.;.;T;T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.11	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;L;.;.;L
MutationTaster	Benign	0.58	D;D;D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.42	N;N;N;N;N;N
REVEL	Benign	0.024
Sift	Benign	0.12	T;T;T;T;T;T
Sift4G	Benign	0.24	T;T;T;T;T;T
Polyphen		0.079	B;B;B;.;.;B
Vest4		0.15
MutPred		0.21		Gain of MoRF binding (P = 0.0973);Gain of MoRF binding (P = 0.0973);Gain of MoRF binding (P = 0.0973);Gain of MoRF binding (P = 0.0973);Gain of MoRF binding (P = 0.0973);Gain of MoRF binding (P = 0.0973);
MVP		0.28
MPC		0.32
ClinPred		0.28	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
gMVP		0.22

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

Other links and lift over

dbSNP: rs1346761723; hg19: chr3-156395664;