rs759795941

Variant names:

• chr10-70533060-G-C
• rs759795941
• NM_014431.3:c.860G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-70533060-G-C
• chr10-70533060-G-T

Variant summary

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

The NM_014431.3(PALD1):​c.860G>C​(p.Ser287Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,580,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: PALD1 NM_014431.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0120
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.122701675).

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.860G>C	p.Ser287Thr	missense	Exon 7 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.860G>C	p.Ser287Thr	missense	Exon 7 of 20	ENSP00000263563.5	Q9ULE6
	PALD1	ENST00000697571.1		c.860G>C	p.Ser287Thr	missense	Exon 7 of 21	ENSP00000513342.1	A0A8V8TMP9
	PALD1	ENST00000893833.1		c.860G>C	p.Ser287Thr	missense	Exon 8 of 21	ENSP00000563892.1

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000259 AC: 5 AN: 193238 AF XY: 0.0000193

Gnomad AFR exome AF: 0.0000853

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: 0.0000366

Gnomad OTH exome AF: 0.000197

GnomAD4 exome AF: 0.000156 AC: 223 AN: 1427916 Hom.: 0 Cov.: 31 AF XY: 0.000126 AC XY: 89 AN XY: 707270

African (AFR) AF: 0.0000610 AC: 2 AN: 32772

American (AMR) AF: 0.00 AC: 0 AN: 40040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25450

East Asian (EAS) AF: 0.00 AC: 0 AN: 37938

South Asian (SAS) AF: 0.00 AC: 0 AN: 81674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.000197 AC: 216 AN: 1094326

Other (OTH) AF: 0.0000847 AC: 5 AN: 59054

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152234 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74374

African (AFR) AF: 0.0000482 AC: 2 AN: 41456

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000167 AC: 2

ClinVar

ClinVar submissions

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	0.086
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M
PhyloP100		-0.012
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.045
Sift	Benign	0.17	T
Sift4G	Benign	0.14	T
Polyphen		0.13	B
Vest4		0.32
MutPred		0.26		Loss of disorder (P = 0.1066)
MVP		0.36
MPC		0.19
ClinPred		0.027	T
GERP RS		1.9
Varity_R		0.038
gMVP		0.38
Mutation Taster		=97/3	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: rs759795941; hg19: chr10-72292816;