Genetic Variant PALD1:p.Thr81Met (chr10-70529285-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014431.3(PALD1):c.242C>T(p.Thr81Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,484,840 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 25)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

PALD1
NM_014431.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.87

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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.242C>T	p.Thr81Met	missense	Exon 3 of 20	NP_055246.2	Q9ULE6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PALD1	ENST00000263563.7	TSL:1 MANE Select	c.242C>T	p.Thr81Met	missense	Exon 3 of 20	ENSP00000263563.5	Q9ULE6
PALD1	ENST00000697571.1		c.242C>T	p.Thr81Met	missense	Exon 3 of 21	ENSP00000513342.1	A0A8V8TMP9
PALD1	ENST00000893833.1		c.242C>T	p.Thr81Met	missense	Exon 4 of 21	ENSP00000563892.1

Frequencies

GnomAD3 genomes

AF:

0.0000145

AC:

AN:

137694

Hom.:

Cov.:

show subpopulations

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:

0.0000307

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000202

AC:

AN:

248014

AF XY:

0.0000224

show subpopulations

Gnomad AFR exome

AF:

0.0000627

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000505

AC:

AN:

1347146

Hom.:

Cov.:

AF XY:

0.0000434

AC XY:

AN XY:

668474

show subpopulations

African (AFR)

AF:

0.0000652

AC:

AN:

30694

American (AMR)

AF:

0.00

AC:

AN:

41534

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21866

East Asian (EAS)

AF:

0.00

AC:

AN:

33170

South Asian (SAS)

AF:

0.0000237

AC:

AN:

84558

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43874

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4952

European-Non Finnish (NFE)

AF:

0.0000619

AC:

AN:

1033468

Other (OTH)

AF:

0.00

AC:

AN:

53030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

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

AF:

0.0000145

AC:

AN:

137694

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

65498

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

37976

American (AMR)

AF:

0.00

AC:

AN:

12004

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3376

East Asian (EAS)

AF:

0.00

AC:

AN:

4338

South Asian (SAS)

AF:

0.00

AC:

AN:

4040

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7858

Middle Eastern (MID)

AF:

0.00

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.0000307

AC:

AN:

65102

Other (OTH)

AF:

0.00

AC:

AN:

1884

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

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:

0.0000284

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

Eigen

Benign

0.17

Eigen_PC

Benign

0.049

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.0

PhyloP100

2.9

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.7

REVEL

Benign

0.10

Sift

Benign

0.051

Sift4G

Uncertain

0.028

Polyphen

0.98

Vest4

0.41

MVP

0.76

MPC

0.69

ClinPred

0.55

GERP RS

2.0

Varity_R

0.036

gMVP

0.35

Mutation Taster

=95/5

polymorphism

(source)

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

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