PWWP3A p.Asp116Glu

Variant names:

• chr19-1360269-C-A
• NM_001369789.1:c.348C>A
• PWWP3A p.Asp116Glu

Your query was ambiguous. Multiple possible variants found:

• chr19-1360269-C-A
• chr19-1360269-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001369789.1(PWWP3A):​c.348C>A​(p.Asp116Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PWWP3A NM_001369789.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04934615).

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.348C>A	p.Asp116Glu	missense	Exon 5 of 14	NP_001356718.1	Q2TAK8-1
	PWWP3A	NM_001369790.1		c.348C>A	p.Asp116Glu	missense	Exon 5 of 15	NP_001356719.1
	PWWP3A	NM_001382408.1		c.348C>A	p.Asp116Glu	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.348C>A	p.Asp116Glu	missense	Exon 5 of 14	ENSP00000467287.4	Q2TAK8-1
	PWWP3A	ENST00000415183.7	TSL:1	c.348C>A	p.Asp116Glu	missense	Exon 4 of 14	ENSP00000394925.3	Q2TAK8-3
	PWWP3A	ENST00000591806.6	TSL:1	c.348C>A	p.Asp116Glu	missense	Exon 4 of 13	ENSP00000467083.2	Q2TAK8-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.022
DANN	Benign	0.26
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.28
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.016
Sift	Benign	0.54	T
Sift4G	Benign	1.0	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.5
Mutation Taster		=99/1	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-1360268;