chr15-44668431-G-A

Position:

• chr15-44668431-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001387263.1(PATL2):​c.1276C>T​(p.Leu426Phe) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PATL2 NM_001387263.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.39

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04169312).
• BP6: Variant 15-44668431-G-A is Benign according to our data. Variant chr15-44668431-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2269926.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PATL2	NM_001387263.1	c.1276C>T	p.Leu426Phe	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.1276C>T	p.Leu426Phe	missense_variant	15/18		NM_001387263.1	ENSP00000508024	A2
PATL2	ENST00000434130.6	c.1276C>T	p.Leu426Phe	missense_variant	13/16	5		ENSP00000416673	A2
PATL2	ENST00000560780.1	c.709C>T	p.Leu237Phe	missense_variant	12/15	2		ENSP00000453695	P2
PATL2	ENST00000558809.1	c.55C>T	p.Leu19Phe	missense_variant	1/3	3		ENSP00000453723

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.66
DEOGEN2	Benign	0.0053	T;T;.;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.59	.;T;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.042	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N;N;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	1.9	N;N;N;N
REVEL	Benign	0.064
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;B;.;.
Vest4		0.096
MutPred		0.56		Gain of helix (P = 0.0034);Gain of helix (P = 0.0034);.;.;
MVP		0.085
MPC		.;3.40522473235E-4;.;.
ClinPred		0.036	T
GERP RS		4.5
Varity_R		0.042
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr15-44960629;