Genetic Variant PATL2:p.Thr425Ile (chr15-44668433-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001387263.1(PATL2):c.1274C>T(p.Thr425Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000214 in 1,399,062 control chromosomes in the GnomAD database, with no homozygous occurrence. 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

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.27

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PATL2	NM_001387263.1 link	c.1274C>T	p.Thr425Ile	missense_variant	Exon 15 of 18	ENST00000682850.1	NP_001374192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PATL2	ENST00000682850.1 link	c.1274C>T	p.Thr425Ile	missense_variant	Exon 15 of 18		NM_001387263.1	ENSP00000508024.1	C9JE40
PATL2	ENST00000434130.6 link	c.1274C>T	p.Thr425Ile	missense_variant	Exon 13 of 16	5		ENSP00000416673.1	C9JE40
PATL2	ENST00000560780.1 link	c.707C>T	p.Thr236Ile	missense_variant	Exon 12 of 15	2		ENSP00000453695.1	H0YMQ2
PATL2	ENST00000558809.1 link	c.53C>T	p.Thr18Ile	missense_variant	Exon 1 of 3	3		ENSP00000453723.1	H0YMS5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000650

AC:

AN:

153940

Hom.:

AF XY:

0.0000122

AC XY:

AN XY:

81692

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:

0.00000214

AC:

AN:

1399062

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

690050

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:

0.0000252

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.27e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Dec 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1274C>T (p.T425I) alteration is located in exon 13 (coding exon 12) of the PATL2 gene. This alteration results from a C to T substitution at nucleotide position 1274, causing the threonine (T) at amino acid position 425 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

Uncertain

0.39

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T;.;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.75

.;T;T;T

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.61

D;D;D;D

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.7

M;M;.;.

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.1

D;D;D;D

REVEL

Benign

0.21

Sift

Uncertain

0.011

D;D;D;D

Sift4G

Uncertain

0.023

D;D;D;D

Polyphen

0.88

P;P;.;.

Vest4

0.40

MutPred

0.69

Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);.;.;

MVP

0.27

MPC

.;3.40522473235E-4;.;.

ClinPred

0.88

GERP RS

4.7

Varity_R

0.16

gMVP

0.33

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