dbSNP rs527946557: PALD1:c.186-5C>A (chr10-70529224-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014431.3(PALD1):c.186-5C>A 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., cov: 12)

Exomes 𝑓: 0.00012 ( 2 hom. )

Consequence

PALD1
NM_014431.3 splice_region, intron

Scores

Splicing: ADA: 0.0001088

Clinical Significance

Not reported in ClinVar

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BS2

High Homozygotes in GnomAdExome4 at 2 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>A		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>A	splice_region intron	N/A	ENSP00000263563.5	Q9ULE6
PALD1	ENST00000697571.1		c.186-5C>A	splice_region intron	N/A	ENSP00000513342.1	A0A8V8TMP9
PALD1	ENST00000893833.1		c.186-5C>A	splice_region intron	N/A	ENSP00000563892.1

Frequencies

GnomAD3 genomes

AF:

0.000101

AC:

AN:

59392

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000147

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000210

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000143

AC:

AN:

76674

AF XY:

0.0000483

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000367

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000557

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000118

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000124

AC:

AN:

241144

Hom.:

Cov.:

AF XY:

0.0000955

AC XY:

AN XY:

136156

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

9060

American (AMR)

AF:

0.000196

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7002

East Asian (EAS)

AF:

0.000688

AC:

AN:

8718

South Asian (SAS)

AF:

0.0000267

AC:

AN:

37410

European-Finnish (FIN)

AF:

0.0000780

AC:

AN:

12822

Middle Eastern (MID)

AF:

0.000686

AC:

AN:

1458

European-Non Finnish (NFE)

AF:

0.000123

AC:

AN:

138062

Other (OTH)

AF:

0.0000884

AC:

AN:

11312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.540

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:

0.000101

AC:

AN:

59468

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

29772

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17352

American (AMR)

AF:

0.000147

AC:

AN:

6816

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1246

East Asian (EAS)

AF:

0.00

AC:

AN:

1898

South Asian (SAS)

AF:

0.00

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:

0.000210

AC:

AN:

23854

Other (OTH)

AF:

0.00

AC:

AN:

784

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.658

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

7.0

(source)

DANN

Benign

0.87

PhyloP100

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.0080

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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