chr10-70532735-A-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_014431.3(PALD1):c.748A>T(p.Thr250Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000111 in 1,614,044 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 1 hom. )
Consequence
PALD1
NM_014431.3 missense
NM_014431.3 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 5.85
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3975678).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PALD1 | NM_014431.3 | c.748A>T | p.Thr250Ser | missense_variant | 6/20 | ENST00000263563.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PALD1 | ENST00000263563.7 | c.748A>T | p.Thr250Ser | missense_variant | 6/20 | 1 | NM_014431.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152164Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000139 AC: 35AN: 251468Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135914
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GnomAD4 exome AF: 0.000109 AC: 160AN: 1461880Hom.: 1 Cov.: 32 AF XY: 0.000131 AC XY: 95AN XY: 727246
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GnomAD4 genome AF: 0.000125 AC: 19AN: 152164Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74328
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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 submitter | clinical testing | Ambry Genetics | Feb 10, 2022 | The c.748A>T (p.T250S) alteration is located in exon 6 (coding exon 5) of the PALD1 gene. This alteration results from a A to T substitution at nucleotide position 748, causing the threonine (T) at amino acid position 250 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at