chr3-122699590-G-A

Variant names:

• chr3-122699590-G-A
• rs370339926
• NM_017554.3:c.1036G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017554.3(PARP14):​c.1036G>A​(p.Asp346Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,613,744 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D346E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: PARP14 NM_017554.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0520

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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.038754165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP14	NM_017554.3	c.1036G>A	p.Asp346Asn	missense_variant	Exon 6 of 17	ENST00000474629.7	NP_060024.2
PARP14	XM_011512929.3	c.1036G>A	p.Asp346Asn	missense_variant	Exon 6 of 10		XP_011511231.1
PARP14	XR_007095695.1	n.1081G>A		non_coding_transcript_exon_variant	Exon 6 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP14	ENST00000474629.7	c.1036G>A	p.Asp346Asn	missense_variant	Exon 6 of 17	1	NM_017554.3	ENSP00000418194.2
PARP14	ENST00000460683.1	n.559G>A		non_coding_transcript_exon_variant	Exon 3 of 14	5		ENSP00000420649.1
PARP14	ENST00000649945.1	n.835+3928G>A		intron_variant	Intron 5 of 15			ENSP00000497854.1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000361 AC: 9 AN: 249188 AF XY: 0.0000444

Gnomad AFR exome AF: 0.0000646

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: 0.0000531

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.000125 AC: 183 AN: 1461542 Hom.: 0 Cov.: 32 AF XY: 0.000128 AC XY: 93 AN XY: 727068

African (AFR) AF: 0.0000597 AC: 2 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

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

European-Non Finnish (NFE) AF: 0.000150 AC: 167 AN: 1111724

Other (OTH) AF: 0.000232 AC: 14 AN: 60368

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152202 Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74340

African (AFR) AF: 0.000241 AC: 10 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

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

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

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

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

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68042

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.000212 Hom.: 0

Bravo AF: 0.000136

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000505 AC: 2

ESP6500EA AF: 0.000120 AC: 1

ExAC AF: 0.0000248 AC: 3

EpiCase AF: 0.000218

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 15, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1036G>A (p.D346N) alteration is located in exon 6 (coding exon 6) of the PARP14 gene. This alteration results from a G to A substitution at nucleotide position 1036, causing the aspartic acid (D) at amino acid position 346 to be replaced by an asparagine (N). 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	0.075
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.052
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.090
Sift	Benign	0.36	T
Sift4G	Benign	0.45	T
Polyphen		0.014	B
Vest4		0.11
MVP		0.33
MPC		0.19
ClinPred		0.033	T
GERP RS		-1.1
Varity_R		0.041
gMVP		0.37
Mutation Taster		=100/0	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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

dbSNP: rs370339926; hg19: chr3-122418437;