Variant 3-130686267-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014602.3(PIK3R4):c.3419A>T(p.Lys1140Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,418 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PIK3R4
NM_014602.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.71

Variant links:

Genes affected

PIK3R4 (HGNC:8982): (phosphoinositide-3-kinase regulatory subunit 4) Predicted to enable protein serine/threonine kinase activity. Involved in positive regulation of phosphatidylinositol 3-kinase activity; receptor catabolic process; and regulation of cytokinesis. Located in late endosome and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

PIK3R4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3R4	NM_014602.3 linkuse as main transcript	c.3419A>T	p.Lys1140Met	missense_variant	15/20	ENST00000356763.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PIK3R4	ENST00000356763.8 linkuse as main transcript	c.3419A>T	p.Lys1140Met	missense_variant	15/20	1	NM_014602.3	P1
PIK3R4	ENST00000512362.5 linkuse as main transcript	n.149A>T		non_coding_transcript_exon_variant	1/5	2
PIK3R4	ENST00000512677.1 linkuse as main transcript	n.324A>T		non_coding_transcript_exon_variant	2/6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251038

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135660

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461418

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2023

The c.3419A>T (p.K1140M) alteration is located in exon 15 (coding exon 14) of the PIK3R4 gene. This alteration results from a A to T substitution at nucleotide position 3419, causing the lysine (K) at amino acid position 1140 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.37

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.23

Eigen

Benign

0.19

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.72

MutationAssessor

Benign

2.0

MutationTaster

Benign

0.93

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.18

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0060

Polyphen

0.98

Vest4

0.58

MutPred

0.48

Loss of ubiquitination at K1140 (P = 0.0224);

MVP

0.49

MPC

0.68

ClinPred

0.87

GERP RS

4.0

Varity_R

0.29

gMVP

0.35

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over