Variant 10-70532644-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014431.3(PALD1):c.657C>G(p.Ser219Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000256 in 1,614,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

PALD1
NM_014431.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.32

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05717188).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALD1	NM_014431.3 linkuse as main transcript	c.657C>G	p.Ser219Arg	missense_variant	6/20	ENST00000263563.7	NP_055246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALD1	ENST00000263563.7 linkuse as main transcript	c.657C>G	p.Ser219Arg	missense_variant	6/20	1	NM_014431.3	ENSP00000263563	P1

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000514

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000151

AC:

AN:

251192

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000255

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000257

AC:

375

AN:

1461796

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

176

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.000312

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000256

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000254

Hom.:

Bravo

AF:

0.000189

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000198

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000237

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 01, 2023

The c.657C>G (p.S219R) alteration is located in exon 6 (coding exon 5) of the PALD1 gene. This alteration results from a C to G substitution at nucleotide position 657, causing the serine (S) at amino acid position 219 to be replaced by an arginine (R). 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

0.20

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.13

DANN

Benign

0.91

DEOGEN2

Benign

0.012

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.75

M_CAP

Benign

0.0071

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.68

N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.4

REVEL

Benign

0.12

Sift

Benign

0.43

Sift4G

Benign

0.079

Polyphen

0.027

Vest4

0.48

MutPred

0.44

Gain of solvent accessibility (P = 0.0584);

MVP

0.40

MPC

0.22

ClinPred

0.082

GERP RS

-9.9

Varity_R

0.15

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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