chr15-44669096-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001387263.1(PATL2):​c.1108G>A​(p.Gly370Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000644 in 1,396,952 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: 0.0000064 ( 0 hom. )

Consequence

PATL2
NM_001387263.1 missense

Scores

11
5
3

Clinical Significance

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

Conservation

PhyloP100: 5.61
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.952

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PATL2NM_001387263.1 linkuse as main transcriptc.1108G>A p.Gly370Arg missense_variant 14/18 ENST00000682850.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PATL2ENST00000682850.1 linkuse as main transcriptc.1108G>A p.Gly370Arg missense_variant 14/18 NM_001387263.1 A2
PATL2ENST00000434130.6 linkuse as main transcriptc.1108G>A p.Gly370Arg missense_variant 12/165 A2
PATL2ENST00000560780.1 linkuse as main transcriptc.541G>A p.Gly181Arg missense_variant 11/152 P2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000660
AC:
1
AN:
151474
Hom.:
0
AF XY:
0.0000124
AC XY:
1
AN XY:
80364
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000171
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000644
AC:
9
AN:
1396952
Hom.:
0
Cov.:
32
AF XY:
0.0000102
AC XY:
7
AN XY:
688790
show subpopulations
Gnomad4 AFR exome
AF:
0.0000317
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000280
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000650
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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
Uncertain significance, criteria provided, single submittercurationSIB Swiss Institute of BioinformaticsApr 16, 2018This 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. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease. -
Pathogenic, no assertion criteria providedliterature onlyOMIMApr 10, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.34
D
BayesDel_noAF
Pathogenic
0.25
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.41
T;T;.
Eigen
Pathogenic
0.72
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.84
.;T;T
M_CAP
Uncertain
0.20
D
MetaRNN
Pathogenic
0.95
D;D;D
MetaSVM
Uncertain
0.15
D
MutationAssessor
Uncertain
2.4
M;M;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.58
T
PROVEAN
Pathogenic
-7.2
D;D;D
REVEL
Pathogenic
0.77
Sift
Uncertain
0.024
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
0.92
P;P;.
Vest4
0.89
MutPred
0.84
Gain of MoRF binding (P = 0.0362);Gain of MoRF binding (P = 0.0362);.;
MVP
0.50
MPC
.;3.40522473235E-4;.
ClinPred
0.94
D
GERP RS
5.6
Varity_R
0.67
gMVP
0.85

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.

Other links and lift over

dbSNP: rs1397500378; hg19: chr15-44961294; API