rs1414650887

Variant names:

• chr9-68780267-T-A
• rs1414650887
• NM_138333.5:c.103T>A

Your query was ambiguous. Multiple possible variants found:

• chr9-68780267-T-A
• chr9-68780267-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138333.5(PABIR1):​c.103T>A​(p.Ser35Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000383 in 1,566,296 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: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PABIR1 NM_138333.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.61
• Publications: 1 publications found

Genes affected

PABIR1 (HGNC:23490): (PP2A Aalpha (PPP2R1A) and B55A (PPP2R2A) interacting phosphatase regulator 1) Enables protein serine/threonine phosphatase inhibitor activity. Involved in mitotic G2/M transition checkpoint; positive regulation of cell growth; and positive regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PIP5K1B (HGNC:8995): (phosphatidylinositol-4-phosphate 5-kinase type 1 beta) Predicted to enable 1-phosphatidylinositol-4-phosphate 5-kinase activity. Predicted to be involved in regulation of phosphatidylinositol 3-kinase signaling. Predicted to act upstream of or within phosphatidylinositol biosynthetic process. Located in uropod. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41866168).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138333.5. 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
	PABIR1	NM_138333.5	MANE Select	c.103T>A	p.Ser35Thr	missense	Exon 1 of 1	NP_612206.5
	PIP5K1B	NM_003558.4	MANE Select	c.-86+37610T>A		intron	N/A	NP_003549.1	O14986-1
	PIP5K1B	NM_001376036.1		c.-86+37610T>A		intron	N/A	NP_001362965.1	O14986-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PABIR1	ENST00000394264.7	TSL:6 MANE Select	c.103T>A	p.Ser35Thr	missense	Exon 1 of 1	ENSP00000377807.5	Q96E09
	PIP5K1B	ENST00000265382.8	TSL:1 MANE Select	c.-86+37610T>A		intron	N/A	ENSP00000265382.2	O14986-1
	PIP5K1B	ENST00000478500.3	TSL:1	n.-86+37610T>A		intron	N/A	ENSP00000435778.1	O14986-2

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151800 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000212 AC: 3 AN: 1414496 Hom.: 0 Cov.: 31 AF XY: 0.00000428 AC XY: 3 AN XY: 700338

African (AFR) AF: 0.00 AC: 0 AN: 31862

American (AMR) AF: 0.00 AC: 0 AN: 37170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22556

East Asian (EAS) AF: 0.00 AC: 0 AN: 39310

South Asian (SAS) AF: 0.00 AC: 0 AN: 78856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5162

European-Non Finnish (NFE) AF: 0.00000275 AC: 3 AN: 1091988

Other (OTH) AF: 0.00 AC: 0 AN: 58076

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151800 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74116

African (AFR) AF: 0.0000242 AC: 1 AN: 41302

American (AMR) AF: 0.00 AC: 0 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67924

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	27
DANN	Uncertain	0.99
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.85	D
M_CAP	Uncertain	0.099	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.33	T
PhyloP100		3.6
PrimateAI	Pathogenic	0.84	D
REVEL	Benign	0.18
MVP		0.32
MPC		1.5
ClinPred		0.97	D
GERP RS		4.0
PromoterAI		0.028	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.44
Mutation Taster		=73/27	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: rs1414650887; hg19: chr9-71395183;