10-70481325-C-G

Variant names:

• chr10-70481325-C-G
• rs7915565
• NM_014431.3:c.-30+2266C>G

Variant summary

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

The NM_014431.3(PALD1):​c.-30+2266C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 152,134 control chromosomes in the GnomAD database, including 39,914 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 0.71 (39914 hom., cov: 32)
• Consequence: PALD1 NM_014431.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.617
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014431.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALD1	NM_014431.3	MANE Select	c.-30+2266C>G		intron	N/A	NP_055246.2	Q9ULE6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALD1	ENST00000263563.7	TSL:1 MANE Select	c.-30+2266C>G		intron	N/A	ENSP00000263563.5	Q9ULE6
	PALD1	ENST00000697571.1		c.-30+2266C>G		intron	N/A	ENSP00000513342.1	A0A8V8TMP9
	PALD1	ENST00000893833.1		c.-111+2266C>G		intron	N/A	ENSP00000563892.1

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108028 AN: 152016 Hom.: 39908 Cov.: 32

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.710 AC: 108072 AN: 152134 Hom.: 39914 Cov.: 32 AF XY: 0.704 AC XY: 52376 AN XY: 74370

African (AFR) AF: 0.531 AC: 22008 AN: 41464

American (AMR) AF: 0.716 AC: 10960 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2437 AN: 3472

East Asian (EAS) AF: 0.438 AC: 2253 AN: 5148

South Asian (SAS) AF: 0.569 AC: 2750 AN: 4830

European-Finnish (FIN) AF: 0.773 AC: 8181 AN: 10590

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.837 AC: 56916 AN: 68010

Other (OTH) AF: 0.740 AC: 1564 AN: 2114

Alfa AF: 0.729 Hom.: 2445

Bravo AF: 0.700

Asia WGS AF: 0.530 AC: 1848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.3
DANN	Benign	0.53
PhyloP100		0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7915565; hg19: chr10-72241081;