15-72265918-C-T

Variant names:

• chr15-72265918-C-T
• rs1050475280
• NM_001323532.2:c.155G>A

Variant summary

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

The NM_001323532.2(PARP6):​c.155G>A​(p.Ser52Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. S52I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PARP6 NM_001323532.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.20
• Publications: 0 publications found

Genes affected

PARP6 (HGNC:26921): (poly(ADP-ribose) polymerase family member 6) Enables protein ADP-ribosylase activity. Involved in protein auto-ADP-ribosylation and protein mono-ADP-ribosylation. [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=0.20729938).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323532.2. 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
	PARP6	NM_001323532.2	MANE Select	c.155G>A	p.Ser52Asn	missense	Exon 5 of 24	NP_001310461.1	Q2NL67-1
	PARP6	NM_001323525.2		c.155G>A	p.Ser52Asn	missense	Exon 5 of 24	NP_001310454.1
	PARP6	NM_001323528.2		c.155G>A	p.Ser52Asn	missense	Exon 5 of 24	NP_001310457.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP6	ENST00000569795.6	TSL:5 MANE Select	c.155G>A	p.Ser52Asn	missense	Exon 5 of 24	ENSP00000456348.1	Q2NL67-1
	PARP6	ENST00000567974.5	TSL:1	c.11G>A	p.Ser4Asn	missense	Exon 1 of 20	ENSP00000455815.1	H3BQK2
	PARP6	ENST00000419739.7	TSL:1	c.155G>A	p.Ser52Asn	missense	Exon 3 of 20	ENSP00000403265.3	F5H3B4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461052 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726890

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111346

Other (OTH) AF: 0.00 AC: 0 AN: 60370

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T
Eigen	Benign	0.055
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.2
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.065
Sift	Benign	0.050	D
Sift4G	Benign	0.14	T
Polyphen		0.13	B
Vest4		0.50
MutPred		0.22		Loss of phosphorylation at S52 (P = 0.0861)
MVP		0.11
MPC		0.41
ClinPred		0.64	D
GERP RS		5.6
PromoterAI		0.028	Neutral
Varity_R		0.20
gMVP		0.54
Mutation Taster		=78/22	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: rs1050475280; hg19: chr15-72558259;