chr15-44666494-G-A

Position:

• chr15-44666494-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001387263.1(PATL2):​c.1511C>T​(p.Thr504Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 3.67

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15495017).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PATL2	NM_001387263.1	c.1511C>T	p.Thr504Ile	missense_variant	17/18	ENST00000682850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PATL2	ENST00000682850.1	c.1511C>T	p.Thr504Ile	missense_variant	17/18		NM_001387263.1	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Apr 06, 2024

The c.1511C>T (p.T504I) alteration is located in exon 15 (coding exon 14) of the PATL2 gene. This alteration results from a C to T substitution at nucleotide position 1511, causing the threonine (T) at amino acid position 504 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	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.051	T;T;.
Eigen	Benign	-0.074
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.58	.;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Benign	0.10
Sift	Benign	0.082	T;T;T
Sift4G	Uncertain	0.033	D;D;D
Polyphen		0.18	B;B;.
Vest4		0.19
MutPred		0.53		Loss of catalytic residue at T504 (P = 0.05);Loss of catalytic residue at T504 (P = 0.05);.;
MVP		0.20
MPC		.;3.40522473235E-4;.
ClinPred		0.48	T
GERP RS		5.9
Varity_R		0.072
gMVP		0.093

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-44958692;