chr15-65260975-C-T

Variant names:

• chr15-65260975-C-T
• rs141607555
• NM_001316943.2:c.743G>A

Variant summary

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

The NM_001316943.2(PARP16):​c.743G>A​(p.Gly248Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,613,720 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: PARP16 NM_001316943.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.78
• Publications: 5 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.

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.743G>A	p.Gly248Glu	missense	Exon 5 of 6	NP_001303872.1	Q8N5Y8-1
	PARP16	NM_017851.6		c.743G>A	p.Gly248Glu	missense	Exon 5 of 6	NP_060321.3
	PARP16	NM_001316944.2		c.398G>A	p.Gly133Glu	missense	Exon 3 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.743G>A	p.Gly248Glu	missense	Exon 5 of 6	ENSP00000496935.1	Q8N5Y8-1
	PARP16	ENST00000261888.10	TSL:1	c.743G>A	p.Gly248Glu	missense	Exon 5 of 6	ENSP00000261888.6	Q8N5Y8-3
	PARP16	ENST00000906476.1		c.860G>A	p.Gly287Glu	missense	Exon 6 of 7	ENSP00000576535.1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152150 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000107 AC: 27 AN: 251444 AF XY: 0.0000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000168 AC: 246 AN: 1461452 Hom.: 1 Cov.: 31 AF XY: 0.000161 AC XY: 117 AN XY: 727052

African (AFR) AF: 0.0000299 AC: 1 AN: 33466

American (AMR) AF: 0.0000224 AC: 1 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86238

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5712

European-Non Finnish (NFE) AF: 0.000210 AC: 234 AN: 1111694

Other (OTH) AF: 0.0000828 AC: 5 AN: 60374

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152268 Hom.: 0 Cov.: 31 AF XY: 0.000107 AC XY: 8 AN XY: 74444

African (AFR) AF: 0.00 AC: 0 AN: 41564

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000242 Hom.: 0

Bravo AF: 0.000159

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000140 AC: 17

EpiCase AF: 0.000436

EpiControl AF: 0.000237

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	0.89
BayesDel_addAF	Benign	-0.00048	T
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.8
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.70
MVP		0.62
MPC		0.72
ClinPred		0.82	D
GERP RS		5.2
Varity_R		0.60
gMVP		0.79
Mutation Taster		=12/88	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

dbSNP: rs141607555; hg19: chr15-65553313; COSMIC: COSV104562123;