chr15-44668367-G-A

Position:

• chr15-44668367-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001387263.1(PATL2):​c.1340C>T​(p.Pro447Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PATL2 NM_001387263.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.91

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4106229).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PATL2	NM_001387263.1	c.1340C>T	p.Pro447Leu	missense_variant	15/18	ENST00000682850.1	NP_001374192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PATL2	ENST00000682850.1	c.1340C>T	p.Pro447Leu	missense_variant	15/18		NM_001387263.1	ENSP00000508024	A2
PATL2	ENST00000434130.6	c.1340C>T	p.Pro447Leu	missense_variant	13/16	5		ENSP00000416673	A2
PATL2	ENST00000560780.1	c.773C>T	p.Pro258Leu	missense_variant	12/15	2		ENSP00000453695	P2
PATL2	ENST00000558809.1	c.119C>T	p.Pro40Leu	missense_variant	1/3	3		ENSP00000453723

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 30, 2023

The c.1340C>T (p.P447L) 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 1340, causing the proline (P) at amino acid position 447 to be replaced by a leucine (L). 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	0.13
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	T;T;.;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.83	.;T;T;T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.41	T;T;T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.8	M;M;.;.
MutationTaster	Benign	0.89	D;D;D
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-4.5	D;D;D;D
REVEL	Benign	0.18
Sift	Benign	0.093	T;T;D;T
Sift4G	Uncertain	0.0080	D;D;D;D
Polyphen		0.98	D;D;.;.
Vest4		0.43
MutPred		0.35		Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);.;.;
MVP		0.47
MPC		.;3.51004323015E-4;.;.
ClinPred		0.91	D
GERP RS		5.2
Varity_R		0.14
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-44960565;