19-49129515-C-T

Position:

• chr19-49129515-C-T

Variant summary

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

The NM_003660.4(PPFIA3):​c.582+61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 1,528,442 control chromosomes in the GnomAD database, including 290,886 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 0.67 (36643 hom., cov: 34)
  • Exomes 𝑓: 0.60 (254243 hom.)
• Consequence: PPFIA3 NM_003660.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPFIA3	NM_003660.4	c.582+61C>T		intron_variant		ENST00000334186.9	NP_003651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPFIA3	ENST00000334186.9	c.582+61C>T		intron_variant		1	NM_003660.4	ENSP00000335614.3

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102151 AN: 152048 Hom.: 36591 Cov.: 34

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.670

GnomAD4 exome AF: 0.602 AC: 828463 AN: 1376276 Hom.: 254243 AF XY: 0.601 AC XY: 408371 AN XY: 679378

Gnomad4 AFR exome AF: 0.924

Gnomad4 AMR exome AF: 0.599

Gnomad4 ASJ exome AF: 0.692

Gnomad4 EAS exome AF: 0.226

Gnomad4 SAS exome AF: 0.588

Gnomad4 FIN exome AF: 0.499

Gnomad4 NFE exome AF: 0.609

Gnomad4 OTH exome AF: 0.606

GnomAD4 genome AF: 0.672 AC: 102256 AN: 152166 Hom.: 36643 Cov.: 34 AF XY: 0.660 AC XY: 49092 AN XY: 74360

Gnomad4 AFR AF: 0.912

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.671

Alfa AF: 0.625 Hom.: 13494

Bravo AF: 0.692

Asia WGS AF: 0.467 AC: 1626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1559155; hg19: chr19-49632772; COSMIC: COSV61949318; COSMIC: COSV61949318;