chr15-65259416-C-T

Variant names:

• chr15-65259416-C-T
• rs34957967
• NM_001316943.2:c.960G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001316943.2(PARP16):​c.960G>A​(p.Ala320Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000473 in 1,614,092 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (2 hom.)
• Consequence: PARP16 NM_001316943.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.842
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 15-65259416-C-T is Benign according to our data. Variant chr15-65259416-C-T is described in ClinVar as Benign. ClinVar VariationId is 714657.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.842 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.960G>A	p.Ala320Ala	synonymous	Exon 6 of 6	NP_001303872.1	Q8N5Y8-1
	PARP16	NM_017851.6		c.963G>A	p.Ala321Ala	synonymous	Exon 6 of 6	NP_060321.3
	PARP16	NM_001316944.2		c.615G>A	p.Ala205Ala	synonymous	Exon 4 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.960G>A	p.Ala320Ala	synonymous	Exon 6 of 6	ENSP00000496935.1	Q8N5Y8-1
	PARP16	ENST00000261888.10	TSL:1	c.963G>A	p.Ala321Ala	synonymous	Exon 6 of 6	ENSP00000261888.6	Q8N5Y8-3
	PARP16	ENST00000906476.1		c.1077G>A	p.Ala359Ala	synonymous	Exon 7 of 7	ENSP00000576535.1

Frequencies

GnomAD3 genomes AF: 0.00220 AC: 335 AN: 152156 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00719

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000632 AC: 159 AN: 251420 AF XY: 0.000405

Gnomad AFR exome AF: 0.00824

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000292 AC: 427 AN: 1461818 Hom.: 2 Cov.: 31 AF XY: 0.000245 AC XY: 178 AN XY: 727224

African (AFR) AF: 0.00893 AC: 299 AN: 33476

American (AMR) AF: 0.000581 AC: 26 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.0000369 AC: 41 AN: 1111958

Other (OTH) AF: 0.000828 AC: 50 AN: 60392

GnomAD4 genome AF: 0.00221 AC: 337 AN: 152274 Hom.: 3 Cov.: 32 AF XY: 0.00216 AC XY: 161 AN XY: 74454

African (AFR) AF: 0.00722 AC: 300 AN: 41566

American (AMR) AF: 0.00190 AC: 29 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00125 Hom.: 0

Bravo AF: 0.00280

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.0
DANN	Benign	0.39
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs34957967; hg19: chr15-65551754; COSMIC: COSV56036182;