10-70572684-T-C

Variant names:

• chr10-70572684-T-C
• rs10999409
• ENST00000697571.1:c.2418+8165T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000697571.1(PALD1):​c.2418+8165T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 152,090 control chromosomes in the GnomAD database, including 19,625 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 0.49 (19625 hom., cov: 32)
• Consequence: PALD1 ENST00000697571.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALD1	ENST00000697571.1	c.2418+8165T>C		intron_variant	Intron 19 of 20			ENSP00000513342.1
PALD1	ENST00000697573.1	c.2262+25238T>C		intron_variant	Intron 18 of 19			ENSP00000513344.1
PALD1	ENST00000697572.1	c.2250+8165T>C		intron_variant	Intron 18 of 18			ENSP00000513343.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74386 AN: 151972 Hom.: 19612 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.469

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.489 AC: 74415 AN: 152090 Hom.: 19625 Cov.: 32 AF XY: 0.492 AC XY: 36598 AN XY: 74346

African (AFR) AF: 0.297 AC: 12319 AN: 41464

American (AMR) AF: 0.451 AC: 6898 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1944 AN: 3464

East Asian (EAS) AF: 0.730 AC: 3780 AN: 5180

South Asian (SAS) AF: 0.509 AC: 2456 AN: 4828

European-Finnish (FIN) AF: 0.643 AC: 6796 AN: 10564

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38585 AN: 67984

Other (OTH) AF: 0.471 AC: 996 AN: 2114

Alfa AF: 0.542 Hom.: 91235

Bravo AF: 0.462

Asia WGS AF: 0.564 AC: 1962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.14
DANN	Benign	0.15
PhyloP100		-1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10999409; hg19: chr10-72332440;