10-70529223-C-G

Variant names:

• chr10-70529223-C-G
• rs200131551
• NM_014431.3:c.186-6C>G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_014431.3(PALD1):​c.186-6C>G variant causes a splice region, 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00020 (1 hom., cov: 13)
  • Exomes 𝑓: 0.00063 (9 hom.)
  • Failed GnomAD Quality Control
• Consequence: PALD1 NM_014431.3 splice_region, intron
• Scores: Splicing: ADA: 0.001483
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALD1	NM_014431.3	c.186-6C>G		splice_region_variant, intron_variant	Intron 2 of 19	ENST00000263563.7	NP_055246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALD1	ENST00000263563.7	c.186-6C>G		splice_region_variant, intron_variant	Intron 2 of 19	1	NM_014431.3	ENSP00000263563.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 14 AN: 69578 Hom.: 1 Cov.: 13 FAILED QC

Gnomad AFR AF: 0.0000523

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000235

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.00202

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000251

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000583 AC: 45 AN: 77240 Hom.: 2 AF XY: 0.000531 AC XY: 22 AN XY: 41464

Gnomad AFR exome AF: 0.000170

Gnomad AMR exome AF: 0.000417

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000169

Gnomad SAS exome AF: 0.00208

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000465

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000629 AC: 169 AN: 268888 Hom.: 9 Cov.: 7 AF XY: 0.000725 AC XY: 109 AN XY: 150356

Gnomad4 AFR exome AF: 0.000526

Gnomad4 AMR exome AF: 0.000426

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000305

Gnomad4 SAS exome AF: 0.00197

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000443

Gnomad4 OTH exome AF: 0.000392

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000201 AC: 14 AN: 69668 Hom.: 1 Cov.: 13 AF XY: 0.000170 AC XY: 6 AN XY: 35204

Gnomad4 AFR AF: 0.0000522

Gnomad4 AMR AF: 0.000234

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00201

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000251

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000206 Hom.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	1.1
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0015
dbscSNV1_RF	Benign	0.046
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;