Genetic Variant PALD1:c.186-5C>G (chr10-70529224-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014431.3(PALD1):c.186-5C>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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00072 ( 1 hom., cov: 12)

Exomes 𝑓: 0.0018 ( 22 hom. )

Consequence

PALD1
NM_014431.3 splice_region, intron

Scores

Splicing: ADA: 0.0001088

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.110

Publications

0 publications found

Variant links:

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]

PALD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 10-70529224-C-G is Benign according to our data. Variant chr10-70529224-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2640552.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 22 AR gene

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.186-5C>G		splice_region intron	N/A	NP_055246.2	Q9ULE6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PALD1	ENST00000263563.7	TSL:1 MANE Select	c.186-5C>G	splice_region intron	N/A	ENSP00000263563.5	Q9ULE6
PALD1	ENST00000697571.1		c.186-5C>G	splice_region intron	N/A	ENSP00000513342.1	A0A8V8TMP9
PALD1	ENST00000893833.1		c.186-5C>G	splice_region intron	N/A	ENSP00000563892.1

Frequencies

GnomAD3 genomes

AF:

0.000724

AC:

AN:

59386

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000983

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000147

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00105

Gnomad SAS

AF:

0.00713

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000629

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00206

AC:

158

AN:

76674

AF XY:

0.00251

show subpopulations

Gnomad AFR exome

AF:

0.00214

Gnomad AMR exome

AF:

0.0000917

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000928

Gnomad FIN exome

AF:

0.000769

Gnomad NFE exome

AF:

0.00203

Gnomad OTH exome

AF:

0.00237

GnomAD4 exome

AF:

0.00182

AC:

439

AN:

241132

Hom.:

Cov.:

AF XY:

0.00225

AC XY:

306

AN XY:

136152

show subpopulations

African (AFR)

AF:

0.00155

AC:

AN:

9056

American (AMR)

AF:

0.000261

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7002

East Asian (EAS)

AF:

0.00115

AC:

AN:

8720

South Asian (SAS)

AF:

0.00596

AC:

223

AN:

37406

European-Finnish (FIN)

AF:

0.000546

AC:

AN:

12822

Middle Eastern (MID)

AF:

0.00480

AC:

AN:

1458

European-Non Finnish (NFE)

AF:

0.00112

AC:

155

AN:

138060

Other (OTH)

AF:

0.00168

AC:

AN:

11310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000723

AC:

AN:

59462

Hom.:

Cov.:

AF XY:

0.000571

AC XY:

AN XY:

29770

show subpopulations

African (AFR)

AF:

0.000980

AC:

AN:

17344

American (AMR)

AF:

0.000147

AC:

AN:

6816

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1246

East Asian (EAS)

AF:

0.00105

AC:

AN:

1898

South Asian (SAS)

AF:

0.00705

AC:

AN:

1134

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5868

Middle Eastern (MID)

AF:

0.00

AC:

AN:

170

European-Non Finnish (NFE)

AF:

0.000629

AC:

AN:

23856

Other (OTH)

AF:

0.00

AC:

AN:

784

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000242

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.4

(source)

DANN

Benign

0.75

PhyloP100

0.11

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.012

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over