rs569729547

Variant names:

• chr15-44669814-C-T
• rs569729547
• NM_001387263.1:c.839G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-44669814-C-T
• chr15-44669814-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001387263.1(PATL2):​c.839G>A​(p.Arg280Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,551,666 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: PATL2 NM_001387263.1 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts P:1 U:2
• Conservation: PhyloP100: 6.58
• Publications: 4 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.

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.839G>A	p.Arg280Gln	missense	Exon 11 of 18	NP_001374192.1	C9JE40
	PATL2	NM_001145112.2		c.839G>A	p.Arg280Gln	missense	Exon 9 of 16	NP_001138584.1	C9JE40
	PATL2	NM_001387261.1		c.839G>A	p.Arg280Gln	missense	Exon 9 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.839G>A	p.Arg280Gln	missense	Exon 11 of 18	ENSP00000508024.1	C9JE40
	PATL2	ENST00000434130.6	TSL:5	c.839G>A	p.Arg280Gln	missense	Exon 9 of 16	ENSP00000416673.1	C9JE40
	PATL2	ENST00000890223.1		c.839G>A	p.Arg280Gln	missense	Exon 10 of 17	ENSP00000560282.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000519 AC: 8 AN: 154012 AF XY: 0.0000612

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000459

Gnomad FIN exome AF: 0.0000655

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000231

GnomAD4 exome AF: 0.0000164 AC: 23 AN: 1399386 Hom.: 0 Cov.: 31 AF XY: 0.0000217 AC XY: 15 AN XY: 690206

African (AFR) AF: 0.0000316 AC: 1 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.000252 AC: 9 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79230

European-Finnish (FIN) AF: 0.0000203 AC: 1 AN: 49268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000927 AC: 10 AN: 1078968

Other (OTH) AF: 0.0000345 AC: 2 AN: 58000

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152280 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74454

African (AFR) AF: 0.00 AC: 0 AN: 41558

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000426 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
1	2	-	Oocyte maturation defect 4 (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.034	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.6
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.35
Sift	Benign	0.11	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.73
MutPred		0.80		Gain of helix (P = 0.0696)
MVP		0.21
MPC		0.00034
ClinPred		0.58	D
GERP RS		4.8
Varity_R		0.24
gMVP		0.44
Mutation Taster		=7/93	disease causing

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

Other links and lift over

dbSNP: rs569729547; hg19: chr15-44962012;