rs2275060

Variant names:

• chr10-70530022-C-T
• rs2275060
• NM_014431.3:c.422C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014431.3(PALD1):​c.422C>T​(p.Ser141Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,577,246 control chromosomes in the GnomAD database, including 31,620 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2548 hom., cov: 32)
  • Exomes 𝑓: 0.20 (29072 hom.)
• Consequence: PALD1 NM_014431.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276
• Publications: 19 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003189385).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALD1	NM_014431.3	c.422C>T	p.Ser141Leu	missense_variant	Exon 4 of 20	ENST00000263563.7	NP_055246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALD1	ENST00000263563.7	c.422C>T	p.Ser141Leu	missense_variant	Exon 4 of 20	1	NM_014431.3	ENSP00000263563.5

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24036 AN: 152106 Hom.: 2552 Cov.: 32

Gnomad AFR AF: 0.0393

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.0867

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.142

GnomAD2 exomes AF: 0.183 AC: 39525 AN: 215880 AF XY: 0.179

Gnomad AFR exome AF: 0.0349

Gnomad AMR exome AF: 0.173

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.234

Gnomad FIN exome AF: 0.323

Gnomad NFE exome AF: 0.200

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.195 AC: 278092 AN: 1425022 Hom.: 29072 Cov.: 33 AF XY: 0.192 AC XY: 135471 AN XY: 706954

African (AFR) AF: 0.0288 AC: 912 AN: 31620

American (AMR) AF: 0.168 AC: 6564 AN: 39168

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 2754 AN: 24004

East Asian (EAS) AF: 0.268 AC: 9950 AN: 37066

South Asian (SAS) AF: 0.0928 AC: 7611 AN: 81980

European-Finnish (FIN) AF: 0.315 AC: 16549 AN: 52482

Middle Eastern (MID) AF: 0.0682 AC: 382 AN: 5604

European-Non Finnish (NFE) AF: 0.204 AC: 222988 AN: 1094476

Other (OTH) AF: 0.177 AC: 10382 AN: 58622

GnomAD4 genome AF: 0.158 AC: 24031 AN: 152224 Hom.: 2548 Cov.: 32 AF XY: 0.161 AC XY: 11986 AN XY: 74414

African (AFR) AF: 0.0392 AC: 1630 AN: 41568

American (AMR) AF: 0.166 AC: 2540 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 433 AN: 3472

East Asian (EAS) AF: 0.239 AC: 1234 AN: 5166

South Asian (SAS) AF: 0.0876 AC: 423 AN: 4828

European-Finnish (FIN) AF: 0.340 AC: 3593 AN: 10574

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13635 AN: 67996

Other (OTH) AF: 0.140 AC: 295 AN: 2112

Alfa AF: 0.182 Hom.: 8051

Bravo AF: 0.143

TwinsUK AF: 0.215 AC: 797

ALSPAC AF: 0.207 AC: 798

ESP6500AA AF: 0.0431 AC: 190

ESP6500EA AF: 0.200 AC: 1720

ExAC AF: 0.172 AC: 20936

Asia WGS AF: 0.162 AC: 563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.8
DANN	Benign	0.88
DEOGEN2	Benign	0.055	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.043	N
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.76	N
PhyloP100		-0.28
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.019
Sift	Benign	0.30	T
Sift4G	Benign	0.099	T
Polyphen		0.0	B
Vest4		0.073
MPC		0.17
ClinPred		0.0033	T
GERP RS		-4.2
Varity_R		0.047
gMVP		0.46
Mutation Taster		=99/1	polymorphism (auto)

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: rs2275060; hg19: chr10-72289778; COSMIC: COSV54972594;