rs35401316

Positions:

• chr10-70604089-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000697571.1(PALD1):​c.*17+5005T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 152,316 control chromosomes in the GnomAD database, including 31 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 0.016 (31 hom., cov: 32)
• Consequence: PALD1 ENST00000697571.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.399

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0156 (2369/152316) while in subpopulation NFE AF= 0.0216 (1471/68018). AF 95% confidence interval is 0.0207. There are 31 homozygotes in gnomad4. There are 1240 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.70604089T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALD1	ENST00000697571.1	c.*17+5005T>C		intron_variant				ENSP00000513342.1
PALD1	ENST00000697573.1	c.*17+5005T>C		intron_variant				ENSP00000513344.1
PALD1	ENST00000697572.1	c.2250+39570T>C		intron_variant				ENSP00000513343.1

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2371 AN: 152198 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.00369

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.0458

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0216

Gnomad OTH AF: 0.0153

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

GnomAD4 genome AF: 0.0156 AC: 2369 AN: 152316 Hom.: 31 Cov.: 32 AF XY: 0.0167 AC XY: 1240 AN XY: 74474

Gnomad4 AFR AF: 0.00368

Gnomad4 AMR AF: 0.0119

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.0458

Gnomad4 NFE AF: 0.0216

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.0196 Hom.: 6

Bravo AF: 0.0124

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.64
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35401316; hg19: chr10-72363845;