9-68780683-C-A

Variant names:

• chr9-68780683-C-A
• NM_138333.5:c.519C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138333.5(PABIR1):​c.519C>A​(p.Ser173Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PABIR1 NM_138333.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.27

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABIR1	NM_138333.5	c.519C>A	p.Ser173Arg	missense_variant	Exon 1 of 1	ENST00000394264.7	NP_612206.5
PIP5K1B	NM_003558.4	c.-85-37778C>A		intron_variant	Intron 2 of 15	ENST00000265382.8	NP_003549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PABIR1	ENST00000394264.7	c.519C>A	p.Ser173Arg	missense_variant	Exon 1 of 1	6	NM_138333.5	ENSP00000377807.5
PIP5K1B	ENST00000265382.8	c.-85-37778C>A		intron_variant	Intron 2 of 15	1	NM_003558.4	ENSP00000265382.2
PIP5K1B	ENST00000478500.3	n.-85-37778C>A		intron_variant	Intron 2 of 20	1		ENSP00000435778.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.519C>A (p.S173R) alteration is located in exon 1 (coding exon 1) of the FAM122A gene. This alteration results from a C to A substitution at nucleotide position 519, causing the serine (S) at amino acid position 173 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Benign	19
DANN	Uncertain	1.0
Eigen	Benign	0.056
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.13	N
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.29	T
PrimateAI	Uncertain	0.76	T
REVEL	Uncertain	0.37
MVP		0.56
MPC		1.7
ClinPred		0.98	D
GERP RS		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-71395599;