Genetic Variant PALD1:c.186-6C>G (chr10-70529223-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014431.3(PALD1):c.186-6C>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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00020 ( 1 hom., cov: 13)

Exomes 𝑓: 0.00063 ( 9 hom. )

Failed GnomAD Quality Control

Consequence

PALD1
NM_014431.3 splice_region, intron

Scores

Splicing: ADA: 0.001483

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0280

Publications

1 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BS2

High Homozygotes in GnomAdExome4 at 9 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.186-6C>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.186-6C>G	splice_region intron	N/A	ENSP00000263563.5	Q9ULE6
PALD1	ENST00000697571.1		c.186-6C>G	splice_region intron	N/A	ENSP00000513342.1	A0A8V8TMP9
PALD1	ENST00000893833.1		c.186-6C>G	splice_region intron	N/A	ENSP00000563892.1

Frequencies

GnomAD3 genomes

AF:

0.000201

AC:

AN:

69578

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000523

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000235

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000388

Gnomad SAS

AF:

0.00202

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000251

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000583

AC:

AN:

77240

AF XY:

0.000531

show subpopulations

Gnomad AFR exome

AF:

0.000170

Gnomad AMR exome

AF:

0.000417

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000169

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000465

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000629

AC:

169

AN:

268888

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

109

AN XY:

150356

show subpopulations

African (AFR)

AF:

0.000526

AC:

AN:

9508

American (AMR)

AF:

0.000426

AC:

AN:

16440

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7580

East Asian (EAS)

AF:

0.000305

AC:

AN:

9846

South Asian (SAS)

AF:

0.00197

AC:

AN:

39608

European-Finnish (FIN)

AF:

0.00

AC:

AN:

13184

Middle Eastern (MID)

AF:

0.000551

AC:

AN:

1816

European-Non Finnish (NFE)

AF:

0.000443

AC:

AN:

158158

Other (OTH)

AF:

0.000392

AC:

AN:

12748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.555

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000201

AC:

AN:

69668

Hom.:

Cov.:

AF XY:

0.000170

AC XY:

AN XY:

35204

show subpopulations

African (AFR)

AF:

0.0000522

AC:

AN:

19168

American (AMR)

AF:

0.000234

AC:

AN:

8550

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1454

East Asian (EAS)

AF:

0.000388

AC:

AN:

2580

South Asian (SAS)

AF:

0.00201

AC:

AN:

1496

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6934

Middle Eastern (MID)

AF:

0.00

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.000251

AC:

AN:

27922

Other (OTH)

AF:

0.00

AC:

AN:

970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.000200

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

1.1

(source)

DANN

Benign

0.72

PhyloP100

0.028

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0015

dbscSNV1_RF

Benign

0.046

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