3-156678236-A-C

Variant names:

• chr3-156678236-A-C
• rs372015234
• NM_015508.5:c.539A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015508.5(TIPARP):​c.539A>C​(p.Lys180Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K180R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TIPARP NM_015508.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2391563).

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.539A>C	p.Lys180Thr	missense	Exon 2 of 6	NP_056323.2
	TIPARP	NM_001184717.1		c.539A>C	p.Lys180Thr	missense	Exon 2 of 6	NP_001171646.1	Q7Z3E1
	TIPARP	NM_001184718.2		c.539A>C	p.Lys180Thr	missense	Exon 2 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.539A>C	p.Lys180Thr	missense	Exon 2 of 6	ENSP00000295924.7	Q7Z3E1
	TIPARP	ENST00000461166.5	TSL:1	c.539A>C	p.Lys180Thr	missense	Exon 2 of 6	ENSP00000420612.1	Q7Z3E1
	TIPARP	ENST00000542783.5	TSL:1	c.539A>C	p.Lys180Thr	missense	Exon 2 of 6	ENSP00000438345.1	Q7Z3E1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.2
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.23
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.036	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.39		Loss of methylation at K180 (P = 0.0013)
MVP		0.65
MPC		1.0
ClinPred		0.84	D
GERP RS		5.1
Varity_R		0.21
gMVP		0.45
Mutation Taster		=85/15	polymorphism

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

dbSNP: rs372015234; hg19: chr3-156396025;