15-65263248-G-A

Variant names:

• chr15-65263248-G-A
• NM_001316943.2:c.592C>T

Variant summary

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

The NM_001316943.2(PARP16):​c.592C>T​(p.His198Tyr) 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. 16/22 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: PARP16 NM_001316943.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.09
• Publications: 0 publications found

Genes affected

PARP16 (HGNC:26040): (poly(ADP-ribose) polymerase family member 16) Enables kinase binding activity; pentosyltransferase activity; and protein serine/threonine kinase activator activity. Involved in several processes, including IRE1-mediated unfolded protein response; positive regulation of protein serine/threonine kinase activity; and protein ADP-ribosylation. Located in endoplasmic reticulum tubular network and nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

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=0.098816305).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001316943.2. 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
	PARP16	NM_001316943.2	MANE Select	c.592C>T	p.His198Tyr	missense	Exon 4 of 6	NP_001303872.1	Q8N5Y8-1
	PARP16	NM_017851.6		c.592C>T	p.His198Tyr	missense	Exon 4 of 6	NP_060321.3
	PARP16	NM_001316944.2		c.247C>T	p.His83Tyr	missense	Exon 2 of 4	NP_001303873.1	Q8N5Y8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP16	ENST00000649807.2	MANE Select	c.592C>T	p.His198Tyr	missense	Exon 4 of 6	ENSP00000496935.1	Q8N5Y8-1
	PARP16	ENST00000261888.10	TSL:1	c.592C>T	p.His198Tyr	missense	Exon 4 of 6	ENSP00000261888.6	Q8N5Y8-3
	PARP16	ENST00000906476.1		c.709C>T	p.His237Tyr	missense	Exon 5 of 7	ENSP00000576535.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Benign	0.074
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	17
DANN	Benign	0.73
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.97	N
PhyloP100		3.1
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.50	N
REVEL	Benign	0.072
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.26
MutPred		0.38		Loss of disorder (P = 0.0505)
MVP		0.27
MPC		0.17
ClinPred		0.059	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.38

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: chr15-65555586;