3-156677987-A-G

Position:

• chr3-156677987-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015508.5(TIPARP):​c.290A>G​(p.Asn97Ser) 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. 15/21 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: 0.736

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.017674446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIPARP	NM_015508.5	c.290A>G	p.Asn97Ser	missense_variant	2/6	ENST00000295924.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIPARP	ENST00000295924.12	c.290A>G	p.Asn97Ser	missense_variant	2/6	1	NM_015508.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Apr 07, 2022

The c.290A>G (p.N97S) alteration is located in exon 2 (coding exon 1) of the TIPARP gene. This alteration results from a A to G substitution at nucleotide position 290, causing the asparagine (N) at amino acid position 97 to be replaced by a serine (S). 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	0.061
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.3
DANN	Benign	0.82
DEOGEN2	Benign	0.090	T;T;T;.;.;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.68	.;.;.;T;T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.018	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.050	N;N;N;.;.;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.65	N;N;N;N;N;N
REVEL	Benign	0.053
Sift	Benign	0.39	T;T;T;T;T;T
Sift4G	Benign	0.93	T;T;T;T;T;T
Polyphen		0.0	B;B;B;.;.;B
Vest4		0.15
MutPred		0.13		Gain of phosphorylation at N97 (P = 0.0396);Gain of phosphorylation at N97 (P = 0.0396);Gain of phosphorylation at N97 (P = 0.0396);Gain of phosphorylation at N97 (P = 0.0396);Gain of phosphorylation at N97 (P = 0.0396);Gain of phosphorylation at N97 (P = 0.0396);
MVP		0.15
MPC		0.21
ClinPred		0.17	T
GERP RS		1.3
Varity_R		0.051
gMVP		0.051

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-156395776;