19-49129515-C-T

Variant names:

• chr19-49129515-C-T
• rs1559155
• NM_003660.4:c.582+61C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003660.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPFIA3	NM_003660.4	MANE Select	c.582+61C>T		intron	N/A	NP_003651.1	O75145-1
	PPFIA3	NR_103842.2		n.776+61C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPFIA3	ENST00000334186.9	TSL:1 MANE Select	c.582+61C>T		intron	N/A	ENSP00000335614.3	O75145-1
	PPFIA3	ENST00000602655.5	TSL:1	n.582+61C>T		intron	N/A	ENSP00000473470.1	R4GN36
	PPFIA3	ENST00000602716.5	TSL:1	n.420+61C>T		intron	N/A

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

African (AFR) AF: 0.924 AC: 28798 AN: 31180

American (AMR) AF: 0.599 AC: 21247 AN: 35498

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 17263 AN: 24964

East Asian (EAS) AF: 0.226 AC: 8028 AN: 35548

South Asian (SAS) AF: 0.588 AC: 46222 AN: 78650

European-Finnish (FIN) AF: 0.499 AC: 24227 AN: 48524

Middle Eastern (MID) AF: 0.623 AC: 2534 AN: 4066

European-Non Finnish (NFE) AF: 0.609 AC: 645493 AN: 1060680

Other (OTH) AF: 0.606 AC: 34651 AN: 57166

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

African (AFR) AF: 0.912 AC: 37913 AN: 41566

American (AMR) AF: 0.590 AC: 9012 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2411 AN: 3472

East Asian (EAS) AF: 0.229 AC: 1187 AN: 5174

South Asian (SAS) AF: 0.578 AC: 2783 AN: 4818

European-Finnish (FIN) AF: 0.488 AC: 5161 AN: 10568

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41606 AN: 67976

Other (OTH) AF: 0.671 AC: 1417 AN: 2112

Alfa AF: 0.625 Hom.: 15028

Bravo AF: 0.692

Asia WGS AF: 0.467 AC: 1626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.75
PhyloP100		-0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1559155; hg19: chr19-49632772; COSMIC: COSV61949318; COSMIC: COSV61949318;