15-44667158-G-T

Variant names:

• chr15-44667158-G-T
• NM_001387263.1:c.1411C>A

Variant summary

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

The NM_001387263.1(PATL2):​c.1411C>A​(p.Leu471Met) variant causes a missense change. The variant allele was found at a frequency of 0.000005 in 1,399,388 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: PATL2 NM_001387263.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.33

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=0.31886214).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PATL2	NM_001387263.1	c.1411C>A	p.Leu471Met	missense_variant	Exon 16 of 18	ENST00000682850.1	NP_001374192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PATL2	ENST00000682850.1	c.1411C>A	p.Leu471Met	missense_variant	Exon 16 of 18		NM_001387263.1	ENSP00000508024.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000500 AC: 7 AN: 1399388 Hom.: 0 Cov.: 30 AF XY: 0.00000435 AC XY: 3 AN XY: 690198

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: 0.00000649

Gnomad4 OTH exome AF: 0.00

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

Oct 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1411C>A (p.L471M) alteration is located in exon 14 (coding exon 13) of the PATL2 gene. This alteration results from a C to A substitution at nucleotide position 1411, causing the leucine (L) at amino acid position 471 to be replaced by a methionine (M). 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	0.10
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T;T;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.69	.;T;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.5	M;M;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.051	T;T;T
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.35
MutPred		0.41		Gain of catalytic residue at L471 (P = 0.0359);Gain of catalytic residue at L471 (P = 0.0359);.;
MVP		0.52
MPC		.;3.61486425784E-4;.
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.28
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr15-44959356;