10-70525962-C-T

Variant summary

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

The NM_014431.3(PALD1):​c.11C>T​(p.Thr4Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,766 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

PALD1
NM_014431.3 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.96
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 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
PALD1NM_014431.3 linkc.11C>T p.Thr4Met missense_variant Exon 2 of 20 ENST00000263563.7 NP_055246.2 Q9ULE6A0A024QZM5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PALD1ENST00000263563.7 linkc.11C>T p.Thr4Met missense_variant Exon 2 of 20 1 NM_014431.3 ENSP00000263563.5 Q9ULE6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250998
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135722
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461766
Hom.:
0
Cov.:
32
AF XY:
0.00000413
AC XY:
3
AN XY:
727176
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 22, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.11C>T (p.T4M) alteration is located in exon 2 (coding exon 1) of the PALD1 gene. This alteration results from a C to T substitution at nucleotide position 11, causing the threonine (T) at amino acid position 4 to be replaced by a methionine (M). 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
Uncertain
0.37
BayesDel_addAF
Benign
-0.097
T
BayesDel_noAF
Benign
-0.28
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.062
T
Eigen
Pathogenic
0.87
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.031
D
MetaRNN
Uncertain
0.69
D
MetaSVM
Benign
-0.63
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Uncertain
0.71
T
PROVEAN
Uncertain
-2.6
D
REVEL
Uncertain
0.29
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0030
D
Polyphen
1.0
D
Vest4
0.74
MutPred
0.17
Loss of glycosylation at T4 (P = 0.0069);
MVP
0.74
MPC
0.70
ClinPred
0.94
D
GERP RS
5.2
Varity_R
0.37
gMVP
0.37

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: rs746010656; hg19: chr10-72285718; COSMIC: COSV54976421; API