10-70529223-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

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, single submitter B:1
• Conservation: PhyloP100: 0.0280

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]

ACMG classification

Verdict is Benign. Variant got -12 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_single_submitter, 1 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	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	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.: 13

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

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.: 7 AF XY: 0.0520 AC XY: 7824 AN XY: 150328

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.: 13 AF XY: 0.0669 AC XY: 2354 AN XY: 35196

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.: 34

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

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

Other links and lift over

dbSNP: rs200131551; hg19: chr10-72288979; COSMIC: COSV54978617;