rs143276983

Variant names:

• chr10-70529285-C-T
• rs143276983
• NM_014431.3:c.242C>T

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.87
• Publications: 0 publications found

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]

ACMG classification

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

Sel.	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: 2 AN: 137694 Hom.: 0 Cov.: 25

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: 5 AN: 248014 AF XY: 0.0000224

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: 68 AN: 1347146 Hom.: 0 Cov.: 30 AF XY: 0.0000434 AC XY: 29 AN XY: 668474

African (AFR) AF: 0.0000652 AC: 2 AN: 30694

American (AMR) AF: 0.00 AC: 0 AN: 41534

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21866

East Asian (EAS) AF: 0.00 AC: 0 AN: 33170

South Asian (SAS) AF: 0.0000237 AC: 2 AN: 84558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43874

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4952

European-Non Finnish (NFE) AF: 0.0000619 AC: 64 AN: 1033468

Other (OTH) AF: 0.00 AC: 0 AN: 53030

GnomAD4 genome AF: 0.0000145 AC: 2 AN: 137694 Hom.: 0 Cov.: 25 AF XY: 0.0000305 AC XY: 2 AN XY: 65498

African (AFR) AF: 0.00 AC: 0 AN: 37976

American (AMR) AF: 0.00 AC: 0 AN: 12004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3376

East Asian (EAS) AF: 0.00 AC: 0 AN: 4338

South Asian (SAS) AF: 0.00 AC: 0 AN: 4040

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7858

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 254

European-Non Finnish (NFE) AF: 0.0000307 AC: 2 AN: 65102

Other (OTH) AF: 0.00 AC: 0 AN: 1884

Alfa AF: 0.0000284 Hom.: 0

Bravo AF: 0.0000189

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.049
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.9
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.10
Sift	Benign	0.051	T
Sift4G	Uncertain	0.028	D
Polyphen		0.98	D
Vest4		0.41
MVP		0.76
MPC		0.69
ClinPred		0.55	D
GERP RS		2.0
Varity_R		0.036
gMVP		0.35
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs143276983; hg19: chr10-72289041; COSMIC: COSV99698640;