rs569729547

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM5PP3_Moderate

The NM_001387263.1(PATL2):ā€‹c.839G>Cā€‹(p.Arg280Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R280Q) has been classified as Pathogenic.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)

Consequence

PATL2
NM_001387263.1 missense

Scores

6
7
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.58
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]

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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;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr15-44669814-C-T is described in Lovd as [Pathogenic].
PP3
MetaRNN computational evidence supports a deleterious effect, 0.922

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PATL2NM_001387263.1 linkuse as main transcriptc.839G>C p.Arg280Pro missense_variant 11/18 ENST00000682850.1 NP_001374192.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PATL2ENST00000682850.1 linkuse as main transcriptc.839G>C p.Arg280Pro missense_variant 11/18 NM_001387263.1 ENSP00000508024 A2
PATL2ENST00000434130.6 linkuse as main transcriptc.839G>C p.Arg280Pro missense_variant 9/165 ENSP00000416673 A2
PATL2ENST00000560780.1 linkuse as main transcriptc.272G>C p.Arg91Pro missense_variant 8/152 ENSP00000453695 P2
PATL2ENST00000558481.5 linkuse as main transcriptc.*268G>C 3_prime_UTR_variant, NMD_transcript_variant 7/75 ENSP00000454201

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.81
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.090
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.094
T;T;.
Eigen
Uncertain
0.28
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.77
.;T;T
M_CAP
Benign
0.038
D
MetaRNN
Pathogenic
0.92
D;D;D
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.3
M;M;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.72
T
PROVEAN
Pathogenic
-4.8
D;D;D
REVEL
Uncertain
0.46
Sift
Benign
0.041
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
0.50
P;P;.
Vest4
0.83
MutPred
0.85
Loss of stability (P = 0.0576);Loss of stability (P = 0.0576);.;
MVP
0.22
MPC
.;3.35281643212E-4;.
ClinPred
0.98
D
GERP RS
4.8
Varity_R
0.83
gMVP
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: rs569729547; hg19: chr15-44962012; API