dbSNP rs1011539285: PATL2:p.Ile318Thr (chr15-44669391-A-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001387263.1(PATL2):c.953T>C(p.Ile318Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,398,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

PATL2
NM_001387263.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 6.52

Variant links:

Genes affected

PATL2 (HGNC:33630): (PAT1 homolog 2) Predicted to enable RNA binding activity. Predicted to be involved in P-body assembly and deadenylation-dependent decapping of nuclear-transcribed mRNA. Predicted to act upstream of or within negative regulation of cytoplasmic mRNA processing body assembly. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PATL2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.823

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PATL2	NM_001387263.1 link	c.953T>C	p.Ile318Thr	missense_variant	Exon 13 of 18	ENST00000682850.1	NP_001374192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PATL2	ENST00000682850.1 link	c.953T>C	p.Ile318Thr	missense_variant	Exon 13 of 18		NM_001387263.1	ENSP00000508024.1	C9JE40
PATL2	ENST00000434130.6 link	c.953T>C	p.Ile318Thr	missense_variant	Exon 11 of 16	5		ENSP00000416673.1	C9JE40
PATL2	ENST00000560780.1 link	c.386T>C	p.Ile129Thr	missense_variant	Exon 10 of 15	2		ENSP00000453695.1	H0YMQ2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000650

AC:

AN:

153936

Hom.:

AF XY:

0.00

AC XY:

AN XY:

81690

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1398784

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689760

show subpopulations

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:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Oocyte maturation defect 4

Pathogenic:1Uncertain:1

Apr 16, 2018

SIB Swiss Institute of Bioinformatics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: curation

This variant is interpreted as a Uncertain Significance, for Oocyte maturation defect 4, Autosomal Recessive inheritance. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS3-Moderate => PS3 downgraded in strength to Moderate (PMID:28965849). -

Apr 10, 2023

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

.;T;T

M_CAP

Benign

0.067

MetaRNN

Pathogenic

0.82

D;D;D

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.7

M;M;.

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

0.97

D;D;.

Vest4

0.62

MutPred

0.74

Loss of stability (P = 0.0078);Loss of stability (P = 0.0078);.;

MVP

0.22

MPC

.;3.40522473235E-4;.

ClinPred

0.88

GERP RS

5.5

Varity_R

0.28

gMVP

0.40

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over