9-68780267-T-G

Variant names:

• chr9-68780267-T-G
• rs1414650887
• NM_138333.5:c.103T>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>G​(p.Ser35Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. S35T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PABIR1 NM_138333.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.61
• Publications: 0 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=0.3681257).

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>G	p.Ser35Ala	missense	Exon 1 of 1	NP_612206.5
	PIP5K1B	NM_003558.4	MANE Select	c.-86+37610T>G		intron	N/A	NP_003549.1	O14986-1
	PIP5K1B	NM_001376036.1		c.-86+37610T>G		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>G	p.Ser35Ala	missense	Exon 1 of 1	ENSP00000377807.5	Q96E09
	PIP5K1B	ENST00000265382.8	TSL:1 MANE Select	c.-86+37610T>G		intron	N/A	ENSP00000265382.2	O14986-1
	PIP5K1B	ENST00000478500.3	TSL:1	n.-86+37610T>G		intron	N/A	ENSP00000435778.1	O14986-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1414496 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 AN: 1091988

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	0.0050	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	27
DANN	Uncertain	0.99
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.62	T
PhyloP100		3.6
PrimateAI	Pathogenic	0.82	D
REVEL	Benign	0.16
MVP		0.30
MPC		0.82
ClinPred		0.97	D
GERP RS		4.0
PromoterAI		-0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.38
Mutation Taster		=70/30	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;