chr19-49129515-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003660.4(PPFIA3):​c.582+61C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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>G		intron	N/A	NP_003651.1	O75145-1
	PPFIA3	NR_103842.2		n.776+61C>G		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>G		intron	N/A	ENSP00000335614.3	O75145-1
	PPFIA3	ENST00000602655.5	TSL:1	n.582+61C>G		intron	N/A	ENSP00000473470.1	R4GN36
	PPFIA3	ENST00000602716.5	TSL:1	n.420+61C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.26e-7 AC: 1 AN: 1377358 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 679956

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000321 AC: 1 AN: 31188

American (AMR) AF: 0.00 AC: 0 AN: 35504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24974

East Asian (EAS) AF: 0.00 AC: 0 AN: 35556

South Asian (SAS) AF: 0.00 AC: 0 AN: 78678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4070

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1061642

Other (OTH) AF: 0.00 AC: 0 AN: 57196

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 15028

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.60
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism

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;