10-70533928-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014431.3(PALD1):​c.877C>T​(p.Pro293Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000764 in 1,596,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

PALD1
NM_014431.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58
Variant links:
Genes affected
PALD1 (HGNC:23530): (phosphatase domain containing paladin 1) Predicted to enable protein tyrosine phosphatase activity. Predicted to be involved in peptidyl-tyrosine dephosphorylation. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14230335).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PALD1NM_014431.3 linkuse as main transcriptc.877C>T p.Pro293Ser missense_variant 8/20 ENST00000263563.7 NP_055246.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PALD1ENST00000263563.7 linkuse as main transcriptc.877C>T p.Pro293Ser missense_variant 8/201 NM_014431.3 ENSP00000263563 P1

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152244
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000549
AC:
13
AN:
236998
Hom.:
0
AF XY:
0.0000624
AC XY:
8
AN XY:
128184
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000305
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000177
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000563
Gnomad OTH exome
AF:
0.000173
GnomAD4 exome
AF:
0.0000776
AC:
112
AN:
1443892
Hom.:
0
Cov.:
31
AF XY:
0.0000963
AC XY:
69
AN XY:
716624
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000233
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000214
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000762
Gnomad4 OTH exome
AF:
0.000134
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152244
Hom.:
0
Cov.:
33
AF XY:
0.0000672
AC XY:
5
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000756
ExAC
AF:
0.0000494
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 22, 2024The c.877C>T (p.P293S) alteration is located in exon 8 (coding exon 7) of the PALD1 gene. This alteration results from a C to T substitution at nucleotide position 877, causing the proline (P) at amino acid position 293 to be replaced by a serine (S). 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
Benign
0.18
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.18
T
Eigen
Benign
-0.15
Eigen_PC
Benign
-0.077
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-3.3
D
REVEL
Benign
0.033
Sift
Benign
0.36
T
Sift4G
Benign
0.11
T
Polyphen
0.29
B
Vest4
0.19
MutPred
0.49
Gain of phosphorylation at P293 (P = 0.0534);
MVP
0.52
MPC
0.48
ClinPred
0.082
T
GERP RS
3.7
Varity_R
0.15
gMVP
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs765966532; hg19: chr10-72293684; API