19-1360270-C-G

Variant names:

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

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>G​(p.Arg117Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 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. R117W) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: PWWP3A NM_001369789.1 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.07364127).

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>G	p.Arg117Gly	missense	Exon 5 of 14	NP_001356718.1	Q2TAK8-1
	PWWP3A	NM_001369790.1		c.349C>G	p.Arg117Gly	missense	Exon 5 of 15	NP_001356719.1
	PWWP3A	NM_001382408.1		c.349C>G	p.Arg117Gly	missense	Exon 5 of 14	NP_001369337.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PWWP3A	ENST00000591337.7	TSL:2 MANE Select	c.349C>G	p.Arg117Gly	missense	Exon 5 of 14	ENSP00000467287.4	Q2TAK8-1
	PWWP3A	ENST00000415183.7	TSL:1	c.349C>G	p.Arg117Gly	missense	Exon 4 of 14	ENSP00000394925.3	Q2TAK8-3
	PWWP3A	ENST00000591806.6	TSL:1	c.349C>G	p.Arg117Gly	missense	Exon 4 of 13	ENSP00000467083.2	Q2TAK8-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74368

African (AFR) AF: 0.0000241 AC: 1 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

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

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

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	0.064
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.44
DANN	Benign	0.71
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.97	T
PhyloP100		-0.27
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.074
Sift	Benign	0.39	T
Sift4G	Benign	0.24	T
Vest4		0.050
MVP		0.25
ClinPred		0.11	T
GERP RS		1.9
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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;