chr10-70533946-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_014431.3(PALD1):​c.895C>T​(p.Arg299Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00306 in 1,607,480 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R299H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0032 ( 11 hom. )

Consequence

PALD1
NM_014431.3 missense

Scores

3
16

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.26
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 Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.008186132).
BP6
Variant 10-70533946-C-T is Benign according to our data. Variant chr10-70533946-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 718337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PALD1NM_014431.3 linkuse as main transcriptc.895C>T p.Arg299Cys missense_variant 8/20 ENST00000263563.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PALD1ENST00000263563.7 linkuse as main transcriptc.895C>T p.Arg299Cys missense_variant 8/201 NM_014431.3 P1

Frequencies

GnomAD3 genomes
AF:
0.00212
AC:
323
AN:
152238
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000579
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000916
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000941
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00398
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.00239
AC:
584
AN:
244842
Hom.:
5
AF XY:
0.00239
AC XY:
317
AN XY:
132604
show subpopulations
Gnomad AFR exome
AF:
0.000628
Gnomad AMR exome
AF:
0.00101
Gnomad ASJ exome
AF:
0.000102
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000670
Gnomad FIN exome
AF:
0.00126
Gnomad NFE exome
AF:
0.00457
Gnomad OTH exome
AF:
0.00101
GnomAD4 exome
AF:
0.00316
AC:
4601
AN:
1455124
Hom.:
11
Cov.:
31
AF XY:
0.00306
AC XY:
2211
AN XY:
723472
show subpopulations
Gnomad4 AFR exome
AF:
0.000663
Gnomad4 AMR exome
AF:
0.000751
Gnomad4 ASJ exome
AF:
0.000232
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000351
Gnomad4 FIN exome
AF:
0.00103
Gnomad4 NFE exome
AF:
0.00391
Gnomad4 OTH exome
AF:
0.00246
GnomAD4 genome
AF:
0.00212
AC:
323
AN:
152356
Hom.:
1
Cov.:
33
AF XY:
0.00172
AC XY:
128
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.000577
Gnomad4 AMR
AF:
0.000915
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000941
Gnomad4 NFE
AF:
0.00398
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00345
Hom.:
0
Bravo
AF:
0.00220
TwinsUK
AF:
0.00431
AC:
16
ALSPAC
AF:
0.00441
AC:
17
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00349
AC:
30
ExAC
AF:
0.00265
AC:
322
EpiCase
AF:
0.00387
EpiControl
AF:
0.00366

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMar 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.094
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
17
DANN
Benign
0.78
DEOGEN2
Benign
0.016
T
Eigen
Benign
-0.98
Eigen_PC
Benign
-0.92
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.75
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.0082
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
0.99
D;D
PrimateAI
Benign
0.32
T
PROVEAN
Uncertain
-2.5
D
REVEL
Benign
0.091
Sift
Benign
0.070
T
Sift4G
Benign
0.17
T
Polyphen
0.012
B
Vest4
0.19
MVP
0.43
MPC
0.26
ClinPred
0.033
T
GERP RS
1.6
Varity_R
0.064
gMVP
0.42

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: rs144523160; hg19: chr10-72293702; API