3-156694120-A-T

Variant names:

• chr3-156694120-A-T
• NM_015508.5:c.1018A>T

Variant summary

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

The NM_015508.5(TIPARP):​c.1018A>T​(p.Asn340Tyr) 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: 32)
• Consequence: TIPARP NM_015508.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.27

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=0.26874527).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIPARP	NM_015508.5	c.1018A>T	p.Asn340Tyr	missense_variant	Exon 3 of 6	ENST00000295924.12	NP_056323.2
TIPARP	NM_001184717.1	c.1018A>T	p.Asn340Tyr	missense_variant	Exon 3 of 6		NP_001171646.1
TIPARP	NM_001184718.2	c.1018A>T	p.Asn340Tyr	missense_variant	Exon 3 of 6		NP_001171647.1
TIPARP	XM_047447935.1	c.1018A>T	p.Asn340Tyr	missense_variant	Exon 3 of 6		XP_047303891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIPARP	ENST00000295924.12	c.1018A>T	p.Asn340Tyr	missense_variant	Exon 3 of 6	1	NM_015508.5	ENSP00000295924.7

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

Oct 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1018A>T (p.N340Y) alteration is located in exon 3 (coding exon 2) of the TIPARP gene. This alteration results from a A to T substitution at nucleotide position 1018, causing the asparagine (N) at amino acid position 340 to be replaced by a tyrosine (Y). 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	0.13
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;T;T;.;.;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.67	.;.;.;T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.27	T;T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.4	L;L;L;.;.;L
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.97	N;N;N;N;N;N
REVEL	Benign	0.081
Sift	Uncertain	0.022	D;D;D;D;D;D
Sift4G	Uncertain	0.040	D;D;D;D;D;D
Polyphen		0.53	P;P;P;.;.;P
Vest4		0.34
MutPred		0.47		Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);
MVP		0.37
MPC		0.52
ClinPred		0.56	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.062
gMVP		0.39

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: chr3-156411909;