Variant 10-70529224-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014431.3(PALD1):c.186-5C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00072 ( 1 hom., cov: 12)

Exomes 𝑓: 0.0018 ( 22 hom. )

Consequence

PALD1
NM_014431.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001088

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.110

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 10-70529224-C-G is Benign according to our data. Variant chr10-70529224-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2640552.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALD1	NM_014431.3 linkuse as main transcript	c.186-5C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		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.186-5C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_014431.3	ENSP00000263563	P1

Frequencies

GnomAD3 genomes

AF:

0.000724

AC:

AN:

59386

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000983

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000147

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00105

Gnomad SAS

AF:

0.00713

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000629

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00206

AC:

158

AN:

76674

Hom.:

AF XY:

0.00251

AC XY:

104

AN XY:

41372

show subpopulations

Gnomad AFR exome

AF:

0.00214

Gnomad AMR exome

AF:

0.0000917

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000928

Gnomad SAS exome

AF:

0.00592

Gnomad FIN exome

AF:

0.000769

Gnomad NFE exome

AF:

0.00203

Gnomad OTH exome

AF:

0.00237

GnomAD4 exome

AF:

0.00182

AC:

439

AN:

241132

Hom.:

Cov.:

AF XY:

0.00225

AC XY:

306

AN XY:

136152

show subpopulations

Gnomad4 AFR exome

AF:

0.00155

Gnomad4 AMR exome

AF:

0.000261

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00115

Gnomad4 SAS exome

AF:

0.00596

Gnomad4 FIN exome

AF:

0.000546

Gnomad4 NFE exome

AF:

0.00112

Gnomad4 OTH exome

AF:

0.00168

GnomAD4 genome

AF:

0.000723

AC:

AN:

59462

Hom.:

Cov.:

AF XY:

0.000571

AC XY:

AN XY:

29770

show subpopulations

Gnomad4 AFR

AF:

0.000980

Gnomad4 AMR

AF:

0.000147

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00105

Gnomad4 SAS

AF:

0.00705

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000629

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000242

Hom.:

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

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

PALD1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.4

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.012

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