chr3-156694076-T-C

Variant names:

• chr3-156694076-T-C
• NM_015508.5:c.974T>C

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIPARP	NM_015508.5	MANE Select	c.974T>C	p.Phe325Ser	missense	Exon 3 of 6	NP_056323.2
	TIPARP	NM_001184717.1		c.974T>C	p.Phe325Ser	missense	Exon 3 of 6	NP_001171646.1	Q7Z3E1
	TIPARP	NM_001184718.2		c.974T>C	p.Phe325Ser	missense	Exon 3 of 6	NP_001171647.1	Q7Z3E1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIPARP	ENST00000295924.12	TSL:1 MANE Select	c.974T>C	p.Phe325Ser	missense	Exon 3 of 6	ENSP00000295924.7	Q7Z3E1
	TIPARP	ENST00000461166.5	TSL:1	c.974T>C	p.Phe325Ser	missense	Exon 3 of 6	ENSP00000420612.1	Q7Z3E1
	TIPARP	ENST00000542783.5	TSL:1	c.974T>C	p.Phe325Ser	missense	Exon 3 of 6	ENSP00000438345.1	Q7Z3E1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.00090
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.5
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.28
Sift	Benign	0.073	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.020	B
Vest4		0.87
MutPred		0.45		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
Mutation Taster		=45/55	disease causing

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

Other links and lift over

hg19: chr3-156411865;