9-68780683-C-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

Scores

3
5
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.27
Variant links:
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]

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ACMG classification

Classification made for transcript

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
PABIR1NM_138333.5 linkc.519C>A p.Ser173Arg missense_variant Exon 1 of 1 ENST00000394264.7 NP_612206.5 Q96E09B3KX07
PIP5K1BNM_003558.4 linkc.-85-37778C>A intron_variant Intron 2 of 15 ENST00000265382.8 NP_003549.1 O14986-1Q7KYT6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PABIR1ENST00000394264.7 linkc.519C>A p.Ser173Arg missense_variant Exon 1 of 1 6 NM_138333.5 ENSP00000377807.5 Q96E09
PIP5K1BENST00000265382.8 linkc.-85-37778C>A intron_variant Intron 2 of 15 1 NM_003558.4 ENSP00000265382.2 O14986-1
PIP5K1BENST00000478500.3 linkn.-85-37778C>A intron_variant Intron 2 of 20 1 ENSP00000435778.1 O14986-2

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
LINK: link

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; API