3-156694076-T-C

Position:

• chr3-156694076-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015508.5(TIPARP):​c.974T>C​(p.Phe325Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TIPARP NM_015508.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.50

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38714272).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIPARP	NM_015508.5	c.974T>C	p.Phe325Ser	missense_variant	3/6	ENST00000295924.12	NP_056323.2
TIPARP	NM_001184717.1	c.974T>C	p.Phe325Ser	missense_variant	3/6		NP_001171646.1
TIPARP	NM_001184718.2	c.974T>C	p.Phe325Ser	missense_variant	3/6		NP_001171647.1
TIPARP	XM_047447935.1	c.974T>C	p.Phe325Ser	missense_variant	3/6		XP_047303891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIPARP	ENST00000295924.12	c.974T>C	p.Phe325Ser	missense_variant	3/6	1	NM_015508.5	ENSP00000295924.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Jan 23, 2023

The c.974T>C (p.F325S) alteration is located in exon 3 (coding exon 2) of the TIPARP gene. This alteration results from a T to C substitution at nucleotide position 974, causing the phenylalanine (F) at amino acid position 325 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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T;T;T;.;.;T
Eigen	Benign	-0.00090
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.75	.;.;.;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.39	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;L;.;.;L
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.98	N;N;N;N;N;N
REVEL	Benign	0.28
Sift	Benign	0.073	T;T;T;T;T;T
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		0.020	B;B;B;.;.;B
Vest4		0.87
MutPred		0.45		Gain of disorder (P = 0.0021);Gain of disorder (P = 0.0021);Gain of disorder (P = 0.0021);Gain of disorder (P = 0.0021);Gain of disorder (P = 0.0021);Gain of disorder (P = 0.0021);
MVP		0.52
MPC		0.57
ClinPred		0.78	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.67

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: chr3-156411865;