Genetic Variant ENST00000602783.1:n.708T>G (chr19-49150749-T-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000602783.1(PPFIA3):n.708T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,942 control chromosomes in the GnomAD database, including 34,535 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.66 ( 34401 hom., cov: 33)

Exomes 𝑓: 0.55 ( 134 hom. )

Consequence

PPFIA3
ENST00000602783.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.60

Publications

9 publications found

Variant links:

Genes affected

PPFIA3 (HGNC:9247): (PTPRF interacting protein alpha 3) The protein encoded by this gene is a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family. Liprins interact with members of LAR family of transmembrane protein tyrosine phosphatases, which are known to be important for axon guidance and mammary gland development. Liprin family protein has been shown to localize phosphatase LAR to cell focal adhesions and may be involved in the molecular organization of presynaptic active zones. [provided by RefSeq, Jul 2008]

PPFIA3 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
PPFIA3-related neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: G2P

PPFIA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPFIA3	NM_003660.4 link	c.*527T>G		3_prime_UTR_variant	Exon 30 of 30	ENST00000334186.9	NP_003651.1	O75145-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPFIA3	ENST00000334186.9 link	c.*527T>G		3_prime_UTR_variant	Exon 30 of 30	1	NM_003660.4	ENSP00000335614.3		O75145-1

Frequencies

GnomAD3 genomes

AF:

0.657

AC:

99825

AN:

151974

Hom.:

34354

Cov.:

show subpopulations

Gnomad AFR

AF:

0.848

Gnomad AMI

AF:

0.743

Gnomad AMR

AF:

0.596

Gnomad ASJ

AF:

0.688

Gnomad EAS

AF:

0.241

Gnomad SAS

AF:

0.587

Gnomad FIN

AF:

0.526

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.608

Gnomad OTH

AF:

0.662

GnomAD4 exome

AF:

0.552

AC:

469

AN:

850

Hom.:

134

Cov.:

AF XY:

0.595

AC XY:

276

AN XY:

464

show subpopulations

African (AFR)

AF:

0.667

AC:

AN:

American (AMR)

AF:

0.482

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.833

AC:

AN:

East Asian (EAS)

AF:

0.222

AC:

AN:

South Asian (SAS)

AF:

0.548

AC:

AN:

European-Finnish (FIN)

AF:

0.577

AC:

AN:

130

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.554

AC:

297

AN:

536

Other (OTH)

AF:

0.583

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.657

AC:

99922

AN:

152092

Hom.:

34401

Cov.:

AF XY:

0.648

AC XY:

48193

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.848

AC:

35233

AN:

41548

American (AMR)

AF:

0.596

AC:

9104

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.688

AC:

2389

AN:

3472

East Asian (EAS)

AF:

0.240

AC:

1230

AN:

5120

South Asian (SAS)

AF:

0.587

AC:

2829

AN:

4818

European-Finnish (FIN)

AF:

0.526

AC:

5567

AN:

10584

Middle Eastern (MID)

AF:

0.588

AC:

173

AN:

294

European-Non Finnish (NFE)

AF:

0.608

AC:

41327

AN:

67954

Other (OTH)

AF:

0.661

AC:

1394

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1626

3252

4879

6505

8131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

778

1556

2334

3112

3890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.500

Hom.:

1443

Bravo

AF:

0.674

Asia WGS

AF:

0.462

AC:

1608

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over