10-70529224-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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

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 -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 GnomAdExome at 3 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000724 AC: 43 AN: 59386 Hom.: 1 Cov.: 12

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.: 3 AF XY: 0.00251 AC XY: 104 AN XY: 41372

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.: 22 Cov.: 6 AF XY: 0.00225 AC XY: 306 AN XY: 136152

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: 43 AN: 59462 Hom.: 1 Cov.: 12 AF XY: 0.000571 AC XY: 17 AN XY: 29770

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.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

Other links and lift over

dbSNP: rs527946557; hg19: chr10-72288980;