rs3781646

Variant names:

• chr11-70344214-G-A
• rs3781646
• NM_003626.5:c.1931+322G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003626.5(PPFIA1):​c.1931+322G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,170 control chromosomes in the GnomAD database, including 2,694 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 0.18 (2694 hom., cov: 32)
• Consequence: PPFIA1 NM_003626.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625
• Publications: 6 publications found

Genes affected

PPFIA1 (HGNC:9245): (PTPRF interacting protein alpha 1) 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. This protein binds to the intracellular membrane-distal phosphatase domain of tyrosine phosphatase LAR, and appears to localize LAR to cell focal adhesions. This interaction may regulate the disassembly of focal adhesion and thus help orchestrate cell-matrix interactions. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

ENSG00000254604 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPFIA1	NM_003626.5	c.1931+322G>A		intron_variant	Intron 15 of 27	ENST00000253925.12	NP_003617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPFIA1	ENST00000253925.12	c.1931+322G>A		intron_variant	Intron 15 of 27	1	NM_003626.5	ENSP00000253925.7

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26656 AN: 152052 Hom.: 2696 Cov.: 32

Gnomad AFR AF: 0.0891

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0889

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.201

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.175 AC: 26664 AN: 152170 Hom.: 2694 Cov.: 32 AF XY: 0.180 AC XY: 13368 AN XY: 74380

African (AFR) AF: 0.0890 AC: 3696 AN: 41540

American (AMR) AF: 0.201 AC: 3079 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 716 AN: 3472

East Asian (EAS) AF: 0.0889 AC: 459 AN: 5162

South Asian (SAS) AF: 0.258 AC: 1244 AN: 4818

European-Finnish (FIN) AF: 0.269 AC: 2844 AN: 10576

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13791 AN: 67986

Other (OTH) AF: 0.204 AC: 431 AN: 2110

Alfa AF: 0.194 Hom.: 3957

Bravo AF: 0.163

Asia WGS AF: 0.184 AC: 639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.90
DANN	Benign	0.44
PhyloP100		-0.63
PromoterAI		0.032	Neutral
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: rs3781646; hg19: chr11-70190320;