3-122695633-C-T

Variant names:

• chr3-122695633-C-T
• rs753993058
• NM_017554.3:c.806C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017554.3(PARP14):​c.806C>T​(p.Ser269Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000879 in 1,593,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: PARP14 NM_017554.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.63
• Publications: 1 publications found

Genes affected

PARP14 (HGNC:29232): (poly(ADP-ribose) polymerase family member 14) This gene encodes a member of the poly(ADP-ribose) polymerase (PARP) protein family. The encoded anti-apoptotic protein may regulate aerobic glycolysis and promote survival of cancer cells. Increased expression of this gene has been reported in a variety of tumor types. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19442797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP14	NM_017554.3	c.806C>T	p.Ser269Leu	missense_variant	Exon 5 of 17	ENST00000474629.7	NP_060024.2
PARP14	XM_011512929.3	c.806C>T	p.Ser269Leu	missense_variant	Exon 5 of 10		XP_011511231.1
PARP14	XR_007095695.1	n.851C>T		non_coding_transcript_exon_variant	Exon 5 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP14	ENST00000474629.7	c.806C>T	p.Ser269Leu	missense_variant	Exon 5 of 17	1	NM_017554.3	ENSP00000418194.2
PARP14	ENST00000460683.1	n.329C>T		non_coding_transcript_exon_variant	Exon 2 of 14	5		ENSP00000420649.1
PARP14	ENST00000649945.1	n.806C>T		non_coding_transcript_exon_variant	Exon 5 of 16			ENSP00000497854.1
PARP14	ENST00000494811.2	c.*7C>T		downstream_gene_variant		4		ENSP00000418535.2

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152104 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000410 AC: 1 AN: 243852 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000906

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000278 AC: 4 AN: 1440992 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 717858

African (AFR) AF: 0.00 AC: 0 AN: 33100

American (AMR) AF: 0.0000451 AC: 2 AN: 44328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25916

East Asian (EAS) AF: 0.00 AC: 0 AN: 39584

South Asian (SAS) AF: 0.00 AC: 0 AN: 85238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1094192

Other (OTH) AF: 0.0000168 AC: 1 AN: 59682

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152104 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74302

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.000655 AC: 10 AN: 15266

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000144

ExAC AF: 0.00000828 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.806C>T (p.S269L) alteration is located in exon 5 (coding exon 5) of the PARP14 gene. This alteration results from a C to T substitution at nucleotide position 806, causing the serine (S) at amino acid position 269 to be replaced by a leucine (L). 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	0.30
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		2.6
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.13
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.16	B
Vest4		0.50
MutPred		0.27		Loss of disorder (P = 0.0349);
MVP		0.67
MPC		0.23
ClinPred		0.86	D
GERP RS		5.5
Varity_R		0.42
gMVP		0.81
Mutation Taster		=68/32	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: rs753993058; hg19: chr3-122414480; COSMIC: COSV71734764; COSMIC: COSV71734764;