Variant 10-70529223-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_014431.3(PALD1):c.186-6C>A 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 Benign (★★).

Frequency

Genomes: 𝑓 0.070 ( 873 hom., cov: 13)

Exomes 𝑓: 0.054 ( 2519 hom. )

Failed GnomAD Quality Control

Consequence

PALD1
NM_014431.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.001613

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0280

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 10-70529223-C-A is Benign according to our data. Variant chr10-70529223-C-A is described in ClinVar as [Benign]. Clinvar id is 768371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALD1	NM_014431.3 linkuse as main transcript	c.186-6C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000263563.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALD1	ENST00000263563.7 linkuse as main transcript	c.186-6C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_014431.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0703

AC:

4894

AN:

69568

Hom.:

871

Cov.:

show subpopulations

Gnomad AFR

AF:

0.186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0344

Gnomad ASJ

AF:

0.0820

Gnomad EAS

AF:

0.00697

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.00332

Gnomad MID

AF:

0.0427

Gnomad NFE

AF:

0.0232

Gnomad OTH

AF:

0.0723

GnomAD3 exomes

AF:

0.0573

AC:

4425

AN:

77240

Hom.:

492

AF XY:

0.0558

AC XY:

2312

AN XY:

41464

show subpopulations

Gnomad AFR exome

AF:

0.262

Gnomad AMR exome

AF:

0.0297

Gnomad ASJ exome

AF:

0.0589

Gnomad EAS exome

AF:

0.0101

Gnomad SAS exome

AF:

0.0941

Gnomad FIN exome

AF:

0.0247

Gnomad NFE exome

AF:

0.0306

Gnomad OTH exome

AF:

0.0475

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0538

AC:

14454

AN:

268840

Hom.:

2519

Cov.:

AF XY:

0.0520

AC XY:

7824

AN XY:

150328

show subpopulations

Gnomad4 AFR exome

AF:

0.261

Gnomad4 AMR exome

AF:

0.0369

Gnomad4 ASJ exome

AF:

0.0757

Gnomad4 EAS exome

AF:

0.0305

Gnomad4 SAS exome

AF:

0.0728

Gnomad4 FIN exome

AF:

0.0194

Gnomad4 NFE exome

AF:

0.0398

Gnomad4 OTH exome

AF:

0.0756

GnomAD4 genome

AF:

0.0705

AC:

4910

AN:

69658

Hom.:

873

Cov.:

AF XY:

0.0669

AC XY:

2354

AN XY:

35196

show subpopulations

Gnomad4 AFR

AF:

0.186

Gnomad4 AMR

AF:

0.0343

Gnomad4 ASJ

AF:

0.0820

Gnomad4 EAS

AF:

0.00736

Gnomad4 SAS

AF:

0.108

Gnomad4 FIN

AF:

0.00332

Gnomad4 NFE

AF:

0.0232

Gnomad4 OTH

AF:

0.0711

Alfa

AF:

0.0106

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

1.5

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0016

dbscSNV1_RF

Benign

0.032

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