Genetic Variant NM_001369789.1:c.167T>C (chr19-1358417-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001369789.1(PWWP3A):c.167T>C(p.Val56Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,820 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PWWP3A
NM_001369789.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.277

Publications

0 publications found

Variant links:

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]

PWWP3A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.072582394).

BP6

Variant 19-1358417-T-C is Benign according to our data. Variant chr19-1358417-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3149992.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PWWP3A	NM_001369789.1	MANE Select	c.167T>C	p.Val56Ala	missense	Exon 4 of 14	NP_001356718.1	Q2TAK8-1
PWWP3A	NM_001369792.1		c.-151T>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 13	NP_001356721.1	Q2TAK8-2
PWWP3A	NM_001369793.1		c.-203T>C		5_prime_UTR_premature_start_codon_gain	Exon 3 of 13	NP_001356722.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PWWP3A	ENST00000591337.7	TSL:2 MANE Select	c.167T>C	p.Val56Ala	missense	Exon 4 of 14	ENSP00000467287.4	Q2TAK8-1
PWWP3A	ENST00000415183.7	TSL:1	c.167T>C	p.Val56Ala	missense	Exon 3 of 14	ENSP00000394925.3	Q2TAK8-3
PWWP3A	ENST00000591806.6	TSL:1	c.167T>C	p.Val56Ala	missense	Exon 3 of 13	ENSP00000467083.2	Q2TAK8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461820

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111976

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.8

(source)

DANN

Benign

0.71

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.39

M_CAP

Benign

0.011

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.0

PhyloP100

0.28

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.4

REVEL

Benign

0.013

Sift

Benign

0.17

Sift4G

Benign

0.38

Vest4

0.11

MVP

0.21

ClinPred

0.057

GERP RS

1.3

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Mutation Taster

=292/8

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over