15-44668397-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001387263.1(PATL2):c.1310C>T(p.Thr437Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 1,551,314 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

PATL2
NM_001387263.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.512

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008596152).

BP6

Variant 15-44668397-G-A is Benign according to our data. Variant chr15-44668397-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2511484.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PATL2	NM_001387263.1 linkuse as main transcript	c.1310C>T	p.Thr437Met	missense_variant	15/18	ENST00000682850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PATL2	ENST00000682850.1 linkuse as main transcript	c.1310C>T	p.Thr437Met	missense_variant	15/18		NM_001387263.1	A2
PATL2	ENST00000434130.6 linkuse as main transcript	c.1310C>T	p.Thr437Met	missense_variant	13/16	5		A2
PATL2	ENST00000560780.1 linkuse as main transcript	c.743C>T	p.Thr248Met	missense_variant	12/15	2		P2
PATL2	ENST00000558809.1 linkuse as main transcript	c.89C>T	p.Thr30Met	missense_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000779

AC:

AN:

153982

Hom.:

AF XY:

0.0000979

AC XY:

AN XY:

81710

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000367

Gnomad SAS exome

AF:

0.000307

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000168

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000465

AC:

AN:

1398984

Hom.:

Cov.:

AF XY:

0.0000594

AC XY:

AN XY:

689982

show subpopulations

Gnomad4 AFR exome

AF:

0.000158

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000140

Gnomad4 SAS exome

AF:

0.000328

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000269

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000656

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000756

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000315

AC:

ExAC

AF:

0.000262

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.68

Cadd

Benign

8.0

Dann

Benign

0.92

DEOGEN2

Benign

0.0043

T;T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0021

M_CAP

Benign

0.0071

MetaRNN

Benign

0.0086

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.1

N;N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

0.39

N;N;N;N

Sift

Benign

0.41

T;T;T;T

Sift4G

Benign

0.29

T;T;T;T

Polyphen

0.015

B;B;.;.

Vest4

0.086

MVP

0.040

MPC

.;3.51004323015E-4;.;.

ClinPred

0.015

GERP RS

1.2

Varity_R

0.020

gMVP

0.15

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