rs1397500378

Variant names:

• chr15-44669096-C-T
• rs1397500378
• NM_001387263.1:c.1108G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001387263.1(PATL2):​c.1108G>A​(p.Gly370Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000644 in 1,396,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: PATL2 NM_001387263.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1
• Conservation: PhyloP100: 5.61
• Publications: 3 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.952

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.1108G>A	p.Gly370Arg	missense	Exon 14 of 18	NP_001374192.1	C9JE40
	PATL2	NM_001145112.2		c.1108G>A	p.Gly370Arg	missense	Exon 12 of 16	NP_001138584.1	C9JE40
	PATL2	NM_001387261.1		c.1108G>A	p.Gly370Arg	missense	Exon 12 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.1108G>A	p.Gly370Arg	missense	Exon 14 of 18	ENSP00000508024.1	C9JE40
	PATL2	ENST00000434130.6	TSL:5	c.1108G>A	p.Gly370Arg	missense	Exon 12 of 16	ENSP00000416673.1	C9JE40
	PATL2	ENST00000890223.1		c.1108G>A	p.Gly370Arg	missense	Exon 13 of 17	ENSP00000560282.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000660 AC: 1 AN: 151474 AF XY: 0.0000124

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000171

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000644 AC: 9 AN: 1396952 Hom.: 0 Cov.: 32 AF XY: 0.0000102 AC XY: 7 AN XY: 688790

African (AFR) AF: 0.0000317 AC: 1 AN: 31546

American (AMR) AF: 0.00 AC: 0 AN: 35382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25014

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35694

South Asian (SAS) AF: 0.00 AC: 0 AN: 78942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00000650 AC: 7 AN: 1077596

Other (OTH) AF: 0.00 AC: 0 AN: 57888

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.41	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.84	T
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.6
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-7.2	D
REVEL	Pathogenic	0.77
Sift	Uncertain	0.024	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.92	P
Vest4		0.89
MutPred		0.84		Gain of MoRF binding (P = 0.0362)
MVP		0.50
MPC		0.00034
ClinPred		0.94	D
GERP RS		5.6
Varity_R		0.67
gMVP		0.85
Mutation Taster		=2/98	disease causing

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

dbSNP: rs1397500378; hg19: chr15-44961294;