19-1360168-G-A

Variant names:

• chr19-1360168-G-A
• rs377193854
• NM_001369789.1:c.247G>A

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.247G>A​(p.Glu83Lys) 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. 14/19 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. E83Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PWWP3A NM_001369789.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.390
• 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: 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=0.18699801).

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.247G>A	p.Glu83Lys	missense	Exon 5 of 14	NP_001356718.1	Q2TAK8-1
	PWWP3A	NM_001369790.1		c.247G>A	p.Glu83Lys	missense	Exon 5 of 15	NP_001356719.1
	PWWP3A	NM_001382408.1		c.247G>A	p.Glu83Lys	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.247G>A	p.Glu83Lys	missense	Exon 5 of 14	ENSP00000467287.4	Q2TAK8-1
	PWWP3A	ENST00000415183.7	TSL:1	c.247G>A	p.Glu83Lys	missense	Exon 4 of 14	ENSP00000394925.3	Q2TAK8-3
	PWWP3A	ENST00000591806.6	TSL:1	c.247G>A	p.Glu83Lys	missense	Exon 4 of 13	ENSP00000467083.2	Q2TAK8-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000454 AC: 1 AN: 220226 AF XY: 0.00

Gnomad AFR exome AF: 0.0000632

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	1.0
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.70	T
PhyloP100		0.39
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.15
Sift	Benign	0.030	D
Sift4G	Uncertain	0.016	D
Vest4		0.22
MVP		0.38
ClinPred		0.56	D
GERP RS		2.4
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs377193854; hg19: chr19-1360167; COSMIC: COSV105141531; COSMIC: COSV105141531;