19-49127991-G-A

Position:

• chr19-49127991-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_003660.4(PPFIA3):​c.118G>A​(p.Glu40Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PPFIA3 NM_003660.4 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.82

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 19-49127991-G-A is Pathogenic according to our data. Variant chr19-49127991-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2582698.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPFIA3	NM_003660.4	c.118G>A	p.Glu40Lys	missense_variant	2/30	ENST00000334186.9	NP_003651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPFIA3	ENST00000334186.9	c.118G>A	p.Glu40Lys	missense_variant	2/30	1	NM_003660.4	ENSP00000335614.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443894 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 718596

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

PPFIA3-related disorder Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

Chao Lab, Baylor College of Medicine, Texas Children's Hospital

Oct 09, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.33	T;T;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.8	L;.;L
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.8	D;.;.
REVEL	Benign	0.27
Sift	Uncertain	0.0020	D;.;.
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.39
MutPred		0.29		Gain of MoRF binding (P = 0.0036);Gain of MoRF binding (P = 0.0036);Gain of MoRF binding (P = 0.0036);
MVP		0.58
MPC		2.9
ClinPred		0.97	D
GERP RS		4.2
Varity_R		0.78
gMVP		0.83

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-49631248;