15-44668982-G-T

Variant names:

• chr15-44668982-G-T
• NM_001387263.1:c.1222C>A

Variant summary

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

The NM_001387263.1(PATL2):​c.1222C>A​(p.Gln408Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000072 in 1,388,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: PATL2 NM_001387263.1 missense, splice_region
• Scores: Splicing: ADA: 0.9537
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.62

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=0.3490069).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PATL2	NM_001387263.1	c.1222C>A	p.Gln408Lys	missense_variant, splice_region_variant	Exon 14 of 18	ENST00000682850.1	NP_001374192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PATL2	ENST00000682850.1	c.1222C>A	p.Gln408Lys	missense_variant, splice_region_variant	Exon 14 of 18		NM_001387263.1	ENSP00000508024.1
PATL2	ENST00000434130.6	c.1222C>A	p.Gln408Lys	missense_variant, splice_region_variant	Exon 12 of 16	5		ENSP00000416673.1
PATL2	ENST00000560780.1	c.655C>A	p.Gln219Lys	missense_variant, splice_region_variant	Exon 11 of 15	2		ENSP00000453695.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1388466 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 683608

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: 9.32e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T;T;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.73	.;T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.9	M;M;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.28
Sift	Uncertain	0.013	D;D;D
Sift4G	Uncertain	0.024	D;D;D
Polyphen		0.92	P;P;.
Vest4		0.24
MutPred		0.72		Gain of ubiquitination at Q408 (P = 0.0203);Gain of ubiquitination at Q408 (P = 0.0203);.;
MVP		0.23
MPC		.;3.40522473235E-4;.
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.27
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.95
dbscSNV1_RF	Pathogenic	0.75
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: chr15-44961180;