chr15-44667155-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.1414G>A​(p.Val472Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PATL2
NM_001387263.1 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.100
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=0.06549111).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PATL2NM_001387263.1 linkuse as main transcriptc.1414G>A p.Val472Ile missense_variant 16/18 ENST00000682850.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PATL2ENST00000682850.1 linkuse as main transcriptc.1414G>A p.Val472Ile missense_variant 16/18 NM_001387263.1 A2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000130
AC:
2
AN:
154052
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
81744
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000810
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000214
AC:
3
AN:
1399372
Hom.:
0
Cov.:
30
AF XY:
0.00000145
AC XY:
1
AN XY:
690194
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000560
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:
0.00
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 07, 2023The c.1414G>A (p.V472I) alteration is located in exon 14 (coding exon 13) of the PATL2 gene. This alteration results from a G to A substitution at nucleotide position 1414, causing the valine (V) at amino acid position 472 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
13
DANN
Benign
0.71
DEOGEN2
Benign
0.0046
T;T;.
Eigen
Benign
-0.89
Eigen_PC
Benign
-0.91
FATHMM_MKL
Benign
0.54
D
LIST_S2
Benign
0.62
.;T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.065
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.9
M;M;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.040
N;N;N
REVEL
Benign
0.074
Sift
Benign
0.27
T;T;T
Sift4G
Benign
0.12
T;T;T
Polyphen
0.016
B;B;.
Vest4
0.041
MutPred
0.57
Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);.;
MVP
0.12
MPC
.;3.66727572043E-4;.
ClinPred
0.049
T
GERP RS
-5.6
Varity_R
0.036
gMVP
0.042

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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: rs1453668266; hg19: chr15-44959353; API