rs1556612

Positions:

• chr10-70567570-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014431.3(PALD1):​c.*837C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,972 control chromosomes in the GnomAD database, including 3,629 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3606 hom., cov: 32)
  • Exomes 𝑓: 0.22 (23 hom.)
• Consequence: PALD1 NM_014431.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALD1	NM_014431.3	c.*837C>T		3_prime_UTR_variant	20/20	ENST00000263563.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALD1	ENST00000263563.7	c.*837C>T		3_prime_UTR_variant	20/20	1	NM_014431.3	P1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 30022 AN: 152084 Hom.: 3592 Cov.: 32

Gnomad AFR AF: 0.0859

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.237

GnomAD4 exome AF: 0.218 AC: 168 AN: 770 Hom.: 23 Cov.: 0 AF XY: 0.222 AC XY: 118 AN XY: 532

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.750

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.429

GnomAD4 genome AF: 0.197 AC: 30039 AN: 152202 Hom.: 3606 Cov.: 32 AF XY: 0.198 AC XY: 14756 AN XY: 74410

Gnomad4 AFR AF: 0.0858

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.234

Alfa AF: 0.219 Hom.: 618

Bravo AF: 0.215

Asia WGS AF: 0.227 AC: 788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs1556612; hg19: chr10-72327326; COSMIC: COSV54971679;