rs3764625

Variant names:

• chr19-49145794-T-G
• rs3764625
• NM_003660.4:c.2746-149T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000334186.9(PPFIA3):​c.2746-149T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 719,468 control chromosomes in the GnomAD database, including 129,468 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 0.64 (33083 hom., cov: 31)
  • Exomes 𝑓: 0.58 (96385 hom.)
• Consequence: PPFIA3 ENST00000334186.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936
• Publications: 18 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000334186.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPFIA3	NM_003660.4	MANE Select	c.2746-149T>G		intron	N/A	NP_003651.1
	PPFIA3	NR_103842.2		n.2717-149T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPFIA3	ENST00000334186.9	TSL:1 MANE Select	c.2746-149T>G		intron	N/A	ENSP00000335614.3
	PPFIA3	ENST00000602848.5	TSL:1	c.22-149T>G		intron	N/A	ENSP00000473418.1
	PPFIA3	ENST00000602655.5	TSL:1	n.*564-149T>G		intron	N/A	ENSP00000473470.1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97760 AN: 151900 Hom.: 33035 Cov.: 31

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.644

GnomAD4 exome AF: 0.575 AC: 326410 AN: 567450 Hom.: 96385 Cov.: 7 AF XY: 0.576 AC XY: 173024 AN XY: 300308

African (AFR) AF: 0.845 AC: 12982 AN: 15366

American (AMR) AF: 0.597 AC: 17838 AN: 29898

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 10174 AN: 15704

East Asian (EAS) AF: 0.242 AC: 8098 AN: 33458

South Asian (SAS) AF: 0.586 AC: 32598 AN: 55648

European-Finnish (FIN) AF: 0.527 AC: 23087 AN: 43840

Middle Eastern (MID) AF: 0.616 AC: 2340 AN: 3798

European-Non Finnish (NFE) AF: 0.593 AC: 201319 AN: 339570

Other (OTH) AF: 0.596 AC: 17974 AN: 30168

GnomAD4 genome AF: 0.644 AC: 97856 AN: 152018 Hom.: 33083 Cov.: 31 AF XY: 0.635 AC XY: 47199 AN XY: 74298

African (AFR) AF: 0.842 AC: 34948 AN: 41490

American (AMR) AF: 0.581 AC: 8869 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2256 AN: 3470

East Asian (EAS) AF: 0.238 AC: 1226 AN: 5146

South Asian (SAS) AF: 0.570 AC: 2738 AN: 4806

European-Finnish (FIN) AF: 0.523 AC: 5534 AN: 10576

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40095 AN: 67956

Other (OTH) AF: 0.643 AC: 1351 AN: 2102

Alfa AF: 0.608 Hom.: 15634

Bravo AF: 0.660

Asia WGS AF: 0.456 AC: 1589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.22
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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: rs3764625; hg19: chr19-49649051; COSMIC: COSV61951251; COSMIC: COSV61951251;