9-68780097-C-G

Position:

• chr9-68780097-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_138333.5(PABIR1):​c.-68C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0507 in 1,457,898 control chromosomes in the GnomAD database, including 2,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (290 hom., cov: 33)
  • Exomes 𝑓: 0.051 (2246 hom.)
• Consequence: PABIR1 NM_138333.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.327

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]

PIP5K1B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018481016).
• BP6: Variant 9-68780097-C-G is Benign according to our data. Variant chr9-68780097-C-G is described in ClinVar as [Benign]. Clinvar id is 770386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PABIR1	NM_138333.5	c.-68C>G		5_prime_UTR_variant	1/1	ENST00000394264.7	NP_612206.5
PIP5K1B	NM_003558.4	c.-86+37440C>G		intron_variant		ENST00000265382.8	NP_003549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PABIR1	ENST00000394264.7	c.-68C>G		5_prime_UTR_variant	1/1	6	NM_138333.5	ENSP00000377807.5
PIP5K1B	ENST00000265382.8	c.-86+37440C>G		intron_variant		1	NM_003558.4	ENSP00000265382.2
PIP5K1B	ENST00000478500.3	n.-86+37440C>G		intron_variant		1		ENSP00000435778.1

Frequencies

GnomAD3 genomes AF: 0.0461 AC: 6988 AN: 151628 Hom.: 286 Cov.: 33

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0327

Gnomad ASJ AF: 0.0517

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0485

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0482

Gnomad OTH AF: 0.0469

GnomAD4 exome AF: 0.0512 AC: 66916 AN: 1306152 Hom.: 2246 Cov.: 30 AF XY: 0.0524 AC XY: 33343 AN XY: 636898

Gnomad4 AFR exome AF: 0.0151

Gnomad4 AMR exome AF: 0.0204

Gnomad4 ASJ exome AF: 0.0532

Gnomad4 EAS exome AF: 0.177

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.0531

Gnomad4 NFE exome AF: 0.0454

Gnomad4 OTH exome AF: 0.0554

GnomAD4 genome AF: 0.0461 AC: 7001 AN: 151746 Hom.: 290 Cov.: 33 AF XY: 0.0494 AC XY: 3664 AN XY: 74136

Gnomad4 AFR AF: 0.0167

Gnomad4 AMR AF: 0.0327

Gnomad4 ASJ AF: 0.0517

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.0485

Gnomad4 NFE AF: 0.0481

Gnomad4 OTH AF: 0.0469

Alfa AF: 0.0104 Hom.: 5

Bravo AF: 0.0430

TwinsUK AF: 0.0423 AC: 157

ALSPAC AF: 0.0446 AC: 172

Asia WGS AF: 0.137 AC: 473 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
CADD	Benign	17
DANN	Benign	0.92
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.0018	T
PROVEAN	Benign	-0.79	N
Sift	Uncertain	0.0030	D
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.055

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

Other links and lift over

dbSNP: rs3750377; hg19: chr9-71395013;