NM_138333.5:c.47C>T

Variant names:

• chr9-68780211-C-T
• rs1554713406
• NM_138333.5:c.47C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_138333.5(PABIR1):​c.47C>T​(p.Thr16Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000794 in 1,384,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000079 (0 hom.)
• Consequence: PABIR1 NM_138333.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0907616).

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.47C>T	p.Thr16Met	missense	Exon 1 of 1	NP_612206.5
	PIP5K1B	NM_003558.4	MANE Select	c.-86+37554C>T		intron	N/A	NP_003549.1	O14986-1
	PIP5K1B	NM_001376036.1		c.-86+37554C>T		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.47C>T	p.Thr16Met	missense	Exon 1 of 1	ENSP00000377807.5	Q96E09
	PIP5K1B	ENST00000265382.8	TSL:1 MANE Select	c.-86+37554C>T		intron	N/A	ENSP00000265382.2	O14986-1
	PIP5K1B	ENST00000478500.3	TSL:1	n.-86+37554C>T		intron	N/A	ENSP00000435778.1	O14986-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000471 AC: 8 AN: 169858 AF XY: 0.0000108

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000369

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000794 AC: 11 AN: 1384722 Hom.: 0 Cov.: 31 AF XY: 0.00000439 AC XY: 3 AN XY: 683010

African (AFR) AF: 0.00 AC: 0 AN: 30484

American (AMR) AF: 0.000360 AC: 11 AN: 30542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20512

East Asian (EAS) AF: 0.00 AC: 0 AN: 39146

South Asian (SAS) AF: 0.00 AC: 0 AN: 72558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080920

Other (OTH) AF: 0.00 AC: 0 AN: 56852

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000252 AC: 3

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	Benign	0.15
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.6
PrimateAI	Uncertain	0.70	T
REVEL	Benign	0.12
MVP		0.16
MPC		1.5
ClinPred		0.22	T
GERP RS		4.1
PromoterAI		-0.094	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.19
Mutation Taster		=93/7	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: rs1554713406; hg19: chr9-71395127;