Variant chr10-70533946-C-T details in Genebe, Genetics Data Aggregator

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

Clinical Significance

Likely benign criteria provided, single submitter B:1

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]

PALD1 links:

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
PALD1	NM_014431.3 linkuse as main transcript	c.895C>T	p.Arg299Cys	missense_variant	8/20	ENST00000263563.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALD1	ENST00000263563.7 linkuse as main transcript	c.895C>T	p.Arg299Cys	missense_variant	8/20	1	NM_014431.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00212

AC:

323

AN:

152238

Hom.:

Cov.:

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.:

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.:

Cov.:

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.:

Cov.:

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.:

Bravo

AF:

0.00220

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00349

AC:

ExAC

AF:

0.00265

AC:

322

EpiCase

AF:

0.00387

EpiControl

AF:

0.00366

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.016

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.92

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.75

M_CAP

Benign

0.012

MetaRNN

Benign

0.0082

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.091

Sift

Benign

0.070

Sift4G

Benign

0.17

Polyphen

0.012

Vest4

0.19

MVP

0.43

MPC

0.26

ClinPred

0.033

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over