chr19-1356401-T-A

Variant names:

• chr19-1356401-T-A
• rs1191768152
• NM_001369789.1:c.9T>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.9T>A​(p.Asp3Glu) 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 152,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: PWWP3A NM_001369789.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.594
• Publications: 1 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=0.20924473).

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.9T>A	p.Asp3Glu	missense	Exon 2 of 14	NP_001356718.1	Q2TAK8-1
	PWWP3A	NM_001369790.1		c.9T>A	p.Asp3Glu	missense	Exon 2 of 15	NP_001356719.1
	PWWP3A	NM_001382408.1		c.9T>A	p.Asp3Glu	missense	Exon 2 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.9T>A	p.Asp3Glu	missense	Exon 2 of 14	ENSP00000467287.4	Q2TAK8-1
	PWWP3A	ENST00000415183.7	TSL:1	c.9T>A	p.Asp3Glu	missense	Exon 1 of 14	ENSP00000394925.3	Q2TAK8-3
	PWWP3A	ENST00000591806.6	TSL:1	c.9T>A	p.Asp3Glu	missense	Exon 1 of 13	ENSP00000467083.2	Q2TAK8-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152256 Hom.: 0 Cov.: 31

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: 152256 Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1 AN XY: 74392

African (AFR) AF: 0.0000241 AC: 1 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

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	0.31
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Uncertain	1.0
Eigen	Benign	0.021
Eigen_PC	Benign	-0.030
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.59
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.13
Sift	Benign	0.24	T
Sift4G	Pathogenic	0.0	D
Vest4		0.57
MVP		0.40
ClinPred		0.55	D
GERP RS		2.5
PromoterAI		0.089	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	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

Other links and lift over

dbSNP: rs1191768152; hg19: chr19-1356400;