NM_001369789.1:c.349C>T

Variant names:

• chr19-1360270-C-T
• rs189340337
• NM_001369789.1:c.349C>T

Variant summary

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

The NM_001369789.1(PWWP3A):​c.349C>T​(p.Arg117Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: PWWP3A NM_001369789.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.268
• Publications: 2 publications found

Genes affected

PWWP3A (HGNC:29641): (PWWP domain containing 3A, DNA repair factor) Enables nucleosome binding activity. Involved in DNA repair and chromatin organization. Located in cytosol and nucleoplasm. [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=0.070168525).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369789.1. 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
	PWWP3A	NM_001369789.1	MANE Select	c.349C>T	p.Arg117Trp	missense	Exon 5 of 14	NP_001356718.1	Q2TAK8-1
	PWWP3A	NM_001369793.1		c.-21C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 13	NP_001356722.1
	PWWP3A	NM_001369790.1		c.349C>T	p.Arg117Trp	missense	Exon 5 of 15	NP_001356719.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PWWP3A	ENST00000591337.7	TSL:2 MANE Select	c.349C>T	p.Arg117Trp	missense	Exon 5 of 14	ENSP00000467287.4	Q2TAK8-1
	PWWP3A	ENST00000415183.7	TSL:1	c.349C>T	p.Arg117Trp	missense	Exon 4 of 14	ENSP00000394925.3	Q2TAK8-3
	PWWP3A	ENST00000591806.6	TSL:1	c.349C>T	p.Arg117Trp	missense	Exon 4 of 13	ENSP00000467083.2	Q2TAK8-1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152214 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.0000119 AC: 3 AN: 251070 AF XY: 0.0000147

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: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461716 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727136

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.0000224 AC: 1 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

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

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111944

Other (OTH) AF: 0.0000331 AC: 2 AN: 60382

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152332 Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2 AN XY: 74496

African (AFR) AF: 0.0000481 AC: 2 AN: 41576

American (AMR) AF: 0.000131 AC: 2 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000247 AC: 3

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	Benign	0.087
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.1
DANN	Uncertain	1.0
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.94	T
PhyloP100		-0.27
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.069
Sift	Benign	0.030	D
Sift4G	Benign	0.067	T
Vest4		0.063
MVP		0.31
ClinPred		0.30	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs189340337; hg19: chr19-1360269; COSMIC: COSV60905506; COSMIC: COSV60905506;