Genetic Variant PALD1:c.186-6C>T (chr10-70529223-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014431.3(PALD1):c.186-6C>T 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 0.0 ( 0 hom., cov: 13)

Exomes 𝑓: 0.000048 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PALD1
NM_014431.3 splice_region, intron

Scores

Splicing: ADA: 0.00003571

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

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>T		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>T	splice_region intron	N/A	ENSP00000263563.5	Q9ULE6
PALD1	ENST00000697571.1		c.186-6C>T	splice_region intron	N/A	ENSP00000513342.1	A0A8V8TMP9
PALD1	ENST00000893833.1		c.186-6C>T	splice_region intron	N/A	ENSP00000563892.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

69584

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000777

AC:

AN:

77240

AF XY:

0.000121

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000169

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000155

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000483

AC:

AN:

268898

Hom.:

Cov.:

AF XY:

0.0000732

AC XY:

AN XY:

150358

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

9508

American (AMR)

AF:

0.00

AC:

AN:

16440

Ashkenazi Jewish (ASJ)

AF:

0.000132

AC:

AN:

7580

East Asian (EAS)

AF:

0.000203

AC:

AN:

9846

South Asian (SAS)

AF:

0.0000252

AC:

AN:

39616

European-Finnish (FIN)

AF:

0.0000758

AC:

AN:

13184

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1816

European-Non Finnish (NFE)

AF:

0.0000506

AC:

AN:

158160

Other (OTH)

AF:

0.00

AC:

AN:

12748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.567

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

69584

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35126

African (AFR)

AF:

0.00

AC:

AN:

19108

American (AMR)

AF:

0.00

AC:

AN:

8528

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1454

East Asian (EAS)

AF:

0.00

AC:

AN:

2582

South Asian (SAS)

AF:

0.00

AC:

AN:

1486

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6934

Middle Eastern (MID)

AF:

0.00

AC:

AN:

234

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

27924

Other (OTH)

AF:

0.00

AC:

AN:

954

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.88

(source)

DANN

Benign

0.92

PhyloP100

0.028

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000036

dbscSNV1_RF

Benign

0.0020

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over