chr12-81347622-T-C

Position:

• chr12-81347622-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_003625.5(PPFIA2):​c.2143A>G​(p.Ser715Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: PPFIA2 NM_003625.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.31

Genes affected

PPFIA2 (HGNC:9246): (PTPRF interacting protein alpha 2) 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. It has been proposed that liprins are multivalent proteins that form complex structures and act as scaffolds for the recruitment and anchoring of LAR family of tyrosine phosphatases. This protein has been shown to bind the calcium/calmodulin-dependent serine protein kinase (MAGUK family) protein (also known as CASK) and proposed to regulate higher-order brain functions in mammals. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

LOC105369872 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, PPFIA2
• BP4: Computational evidence support a benign effect (MetaRNN=0.19684806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPFIA2	NM_003625.5	c.2143A>G	p.Ser715Gly	missense_variant	18/33	ENST00000549396.6
LOC105369872	XR_945148.3	n.149-2668T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPFIA2	ENST00000549396.6	c.2143A>G	p.Ser715Gly	missense_variant	18/33	1	NM_003625.5	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461614 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727096

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: 0.0000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	27
DANN	Uncertain	0.99
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.83	T;T;T;T;T;T;T;T;.;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.82	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.0	N;N;N;N;N;.;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.12	T;T;T;T;T;.;T;T;T;T
Sift4G	Benign	0.38	T;T;T;T;T;T;T;T;T;T
Polyphen		0.92	.;P;.;.;.;.;.;.;.;.
Vest4		0.35
MutPred		0.16		.;Loss of phosphorylation at S715 (P = 0.0065);Loss of phosphorylation at S715 (P = 0.0065);.;.;.;.;Loss of phosphorylation at S715 (P = 0.0065);.;Loss of phosphorylation at S715 (P = 0.0065);
MVP		0.50
MPC		0.36
ClinPred		0.81	D
GERP RS		5.5
Varity_R		0.29
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr12-81741401;