NM_001387263.1:c.1511C>T

Variant names:

• chr15-44666494-G-A
• NM_001387263.1:c.1511C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• oocyte maturation defect 4

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387263.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PATL2	NM_001387263.1	MANE Select	c.1511C>T	p.Thr504Ile	missense	Exon 17 of 18	NP_001374192.1	C9JE40
	PATL2	NM_001145112.2		c.1511C>T	p.Thr504Ile	missense	Exon 15 of 16	NP_001138584.1	C9JE40
	PATL2	NM_001387261.1		c.1511C>T	p.Thr504Ile	missense	Exon 15 of 16	NP_001374190.1	C9JE40

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PATL2	ENST00000682850.1	MANE Select	c.1511C>T	p.Thr504Ile	missense	Exon 17 of 18	ENSP00000508024.1	C9JE40
	PATL2	ENST00000434130.6	TSL:5	c.1511C>T	p.Thr504Ile	missense	Exon 15 of 16	ENSP00000416673.1	C9JE40
	PATL2	ENST00000890223.1		c.1511C>T	p.Thr504Ile	missense	Exon 16 of 17	ENSP00000560282.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.074
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.7
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.10
Sift	Benign	0.082	T
Sift4G	Uncertain	0.033	D
Polyphen		0.18	B
Vest4		0.19
MutPred		0.53		Loss of catalytic residue at T504 (P = 0.05)
MVP		0.20
MPC		0.00034
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

Other links and lift over

hg19: chr15-44958692;