rs758913806

Variant names:

• chr3-130679386-C-A
• rs758913806
• NM_014602.3:c.4006G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-130679386-C-A
• chr3-130679386-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014602.3(PIK3R4):​c.4006G>T​(p.Ala1336Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1336T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIK3R4 NM_014602.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.67
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014602.3. 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
	PIK3R4	NM_014602.3	MANE Select	c.4006G>T	p.Ala1336Ser	missense	Exon 20 of 20	NP_055417.1	Q99570

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3R4	ENST00000356763.8	TSL:1 MANE Select	c.4006G>T	p.Ala1336Ser	missense	Exon 20 of 20	ENSP00000349205.3	Q99570
	PIK3R4	ENST00000954554.1		c.4012G>T	p.Ala1338Ser	missense	Exon 20 of 20	ENSP00000624613.1
	PIK3R4	ENST00000893860.1		c.3997G>T	p.Ala1333Ser	missense	Exon 20 of 20	ENSP00000563919.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	0.0089	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.92	L
PhyloP100		5.7
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.22
Sift	Benign	0.33	T
Sift4G	Benign	0.38	T
Polyphen		0.80	P
Vest4		0.63
MutPred		0.71		Gain of sheet (P = 0.0827)
MVP		0.54
MPC		0.55
ClinPred		0.91	D
GERP RS		5.5
Varity_R		0.15
gMVP		0.42
Mutation Taster		=78/22	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: rs758913806; hg19: chr3-130398230;