Variant 15-44668982-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001387263.1(PATL2):c.1222C>G(p.Gln408Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000418 in 1,540,614 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00043 ( 1 hom. )

Consequence

PATL2
NM_001387263.1 missense, splice_region

Scores

Splicing: ADA: 0.06631

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.62

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03733051).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PATL2	NM_001387263.1 linkuse as main transcript	c.1222C>G	p.Gln408Glu	missense_variant, splice_region_variant	14/18	ENST00000682850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PATL2	ENST00000682850.1 linkuse as main transcript	c.1222C>G	p.Gln408Glu	missense_variant, splice_region_variant	14/18		NM_001387263.1	A2
PATL2	ENST00000434130.6 linkuse as main transcript	c.1222C>G	p.Gln408Glu	missense_variant, splice_region_variant	12/16	5		A2
PATL2	ENST00000560780.1 linkuse as main transcript	c.655C>G	p.Gln219Glu	missense_variant, splice_region_variant	11/15	2		P2

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000544

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000150

AC:

AN:

146368

Hom.:

AF XY:

0.000181

AC XY:

AN XY:

77410

show subpopulations

Gnomad AFR exome

AF:

0.000127

Gnomad AMR exome

AF:

0.0000845

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:

0.000339

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000430

AC:

597

AN:

1388468

Hom.:

Cov.:

AF XY:

0.000414

AC XY:

283

AN XY:

683610

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000144

Gnomad4 ASJ exome

AF:

0.0000410

Gnomad4 EAS exome

AF:

0.0000281

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000536

Gnomad4 OTH exome

AF:

0.000261

GnomAD4 genome

AF:

0.000309

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000384

Hom.:

Bravo

AF:

0.000431

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.000125

AC:

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 submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

PATL2: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.47

Cadd

Benign

Dann

Benign

0.43

DEOGEN2

Benign

0.0067

T;T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.089

FATHMM_MKL

Uncertain

0.80

M_CAP

Benign

0.011

MetaRNN

Benign

0.037

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L;.

MutationTaster

Benign

0.91

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.21

N;N;N

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.89

T;T;T

Polyphen

0.053

B;B;.

Vest4

0.10

MVP

0.072

MPC

.;3.40522473235E-4;.

ClinPred

0.049

GERP RS

5.7

Varity_R

0.16

gMVP

0.082

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.066

dbscSNV1_RF

Benign

0.34

SpliceAI score (max)

0.11

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