chr15-44668999-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001387263.1(PATL2):​c.1205G>A​(p.Arg402Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000484 in 1,548,254 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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: 32)
Exomes 𝑓: 0.000050 ( 1 hom. )

Consequence

PATL2
NM_001387263.1 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.249
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_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.042292953).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PATL2NM_001387263.1 linkuse as main transcriptc.1205G>A p.Arg402Gln missense_variant 14/18 ENST00000682850.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PATL2ENST00000682850.1 linkuse as main transcriptc.1205G>A p.Arg402Gln missense_variant 14/18 NM_001387263.1 A2
PATL2ENST00000434130.6 linkuse as main transcriptc.1205G>A p.Arg402Gln missense_variant 12/165 A2
PATL2ENST00000560780.1 linkuse as main transcriptc.638G>A p.Arg213Gln missense_variant 11/152 P2

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000106
AC:
16
AN:
151264
Hom.:
0
AF XY:
0.0000873
AC XY:
7
AN XY:
80168
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000452
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000896
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000514
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000501
AC:
70
AN:
1395970
Hom.:
1
Cov.:
32
AF XY:
0.0000465
AC XY:
32
AN XY:
688256
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000340
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000280
Gnomad4 SAS exome
AF:
0.000152
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000418
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152284
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000224
Hom.:
0
Bravo
AF:
0.0000604
ExAC
AF:
0.0000825
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenDec 01, 2023PATL2: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.068
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
14
DANN
Benign
0.96
DEOGEN2
Benign
0.040
T;T;.
Eigen
Benign
-0.95
Eigen_PC
Benign
-0.98
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.77
.;T;T
M_CAP
Benign
0.033
D
MetaRNN
Benign
0.042
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L;L;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-1.1
N;N;N
REVEL
Benign
0.033
Sift
Benign
0.19
T;T;T
Sift4G
Benign
0.26
T;T;T
Polyphen
0.28
B;B;.
Vest4
0.065
MutPred
0.48
Loss of helix (P = 0.2022);Loss of helix (P = 0.2022);.;
MVP
0.076
MPC
.;3.40522473235E-4;.
ClinPred
0.038
T
GERP RS
-0.88
Varity_R
0.041
gMVP
0.13

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: rs199627539; hg19: chr15-44961197; COSMIC: COSV101436313; COSMIC: COSV101436313; API