Variant 11-59647769-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM1BS2

The NM_152716.3(PATL1):c.1878G>T(p.Lys626Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,636 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

PATL1
NM_152716.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.49

Variant links:

Genes affected

PATL1 (HGNC:26721): (PAT1 homolog 1, processing body mRNA decay factor) Enables poly(G) binding activity and poly(U) RNA binding activity. Involved in P-body assembly and deadenylation-dependent decapping of nuclear-transcribed mRNA. Located in P-body and cytosol. Colocalizes with CCR4-NOT complex. [provided by Alliance of Genome Resources, Apr 2022]

PATL1 links:

PATL1 (HGNC:):

PATL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM1

In a mutagenesis_site In mut1; Abolishes RNA-binding, localization to P-body and interaction with the decapping machinery; when associated with A-519; A-520; A-591; A-595 and A-625. (size 0) in uniprot entity PATL1_HUMAN

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PATL1	NM_152716.3 linkuse as main transcript	c.1878G>T	p.Lys626Asn	missense_variant	15/19	ENST00000300146.10	NP_689929.2	Q86TB9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PATL1	ENST00000300146.10 linkuse as main transcript	c.1878G>T	p.Lys626Asn	missense_variant	15/19	1	NM_152716.3	ENSP00000300146.9		Q86TB9-1
PATL1	ENST00000531919.1 linkuse as main transcript	n.118G>T		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249186

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135180

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461636

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727094

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

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

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 28, 2024

The c.1878G>T (p.K626N) alteration is located in exon 15 (coding exon 15) of the PATL1 gene. This alteration results from a G to T substitution at nucleotide position 1878, causing the lysine (K) at amino acid position 626 to be replaced by an asparagine (N). 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

Pathogenic

1.0

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.037

MetaRNN

Uncertain

0.71

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.26

Sift

Benign

0.18

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.79

MutPred

0.46

Loss of ubiquitination at K626 (P = 0.0148);

MVP

0.20

MPC

1.1

ClinPred

0.96

GERP RS

4.1

Varity_R

0.73

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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