rs3764625

Positions:

• chr19-49145794-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003660.4(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 NM_003660.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPFIA3	NM_003660.4	c.2746-149T>G		intron_variant		ENST00000334186.9	NP_003651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPFIA3	ENST00000334186.9	c.2746-149T>G		intron_variant		1	NM_003660.4	ENSP00000335614.3

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

Gnomad4 AFR exome AF: 0.845

Gnomad4 AMR exome AF: 0.597

Gnomad4 ASJ exome AF: 0.648

Gnomad4 EAS exome AF: 0.242

Gnomad4 SAS exome AF: 0.586

Gnomad4 FIN exome AF: 0.527

Gnomad4 NFE exome AF: 0.593

Gnomad4 OTH exome AF: 0.596

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

Gnomad4 AFR AF: 0.842

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.643

Alfa AF: 0.606 Hom.: 13922

Bravo AF: 0.660

Asia WGS AF: 0.456 AC: 1589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.22

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

LitVar

Other links and lift over

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