rs1057520141

Variant names:

• chr12-42460268-T-A
• NM_153026.3:c.2037A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-42460268-T-A
• chr12-42460268-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153026.3(PRICKLE1):​c.2037A>T​(p.Arg679Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PRICKLE1 NM_153026.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.961

Genes affected

PRICKLE1 (HGNC:17019): (prickle planar cell polarity protein 1) This gene encodes a nuclear receptor that may be a negative regulator of the Wnt/beta-catenin signaling pathway. The encoded protein localizes to the nuclear membrane and has been implicated in the nuclear trafficking of the transcription repressors REST/NRSF and REST4. Mutations in this gene have been linked to progressive myoclonus epilepsy. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 3. [provided by RefSeq, Sep 2009]

ENSG00000257225 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29378664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRICKLE1	NM_153026.3	c.2037A>T	p.Arg679Ser	missense_variant	Exon 8 of 8	ENST00000345127.9	NP_694571.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRICKLE1	ENST00000345127.9	c.2037A>T	p.Arg679Ser	missense_variant	Exon 8 of 8	1	NM_153026.3	ENSP00000345064.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Uncertain	0.57	D;D;D;D;D;D;D;D;D;D
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.24	N
LIST_S2	Pathogenic	0.98	.;.;.;.;.;.;.;.;.;D
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.29	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.4	M;M;M;M;M;M;M;M;M;M
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.9	D;.;D;.;D;.;.;D;.;D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0010	D;.;D;.;D;.;.;D;.;D
Sift4G	Uncertain	0.0060	D;.;D;.;D;.;.;D;.;D
Polyphen		0.91	P;P;P;P;P;P;P;P;P;P
Vest4		0.65
MutPred		0.39		Gain of phosphorylation at R679 (P = 2e-04);Gain of phosphorylation at R679 (P = 2e-04);Gain of phosphorylation at R679 (P = 2e-04);Gain of phosphorylation at R679 (P = 2e-04);Gain of phosphorylation at R679 (P = 2e-04);Gain of phosphorylation at R679 (P = 2e-04);Gain of phosphorylation at R679 (P = 2e-04);Gain of phosphorylation at R679 (P = 2e-04);Gain of phosphorylation at R679 (P = 2e-04);Gain of phosphorylation at R679 (P = 2e-04);
MVP		0.60
MPC		1.2
ClinPred		0.99	D
GERP RS		-4.4
Varity_R		0.74
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-42854070;