chr15-44668359-C-T

Variant names:

• chr15-44668359-C-T
• rs760378079
• NM_001387263.1:c.1348G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NM_001387263.1(PATL2):​c.1348G>A​(p.Val450Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,550,842 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (1 hom.)
• Consequence: PATL2 NM_001387263.1 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.520
• Publications: 0 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_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0070055425).
• BP6: Variant 15-44668359-C-T is Benign according to our data. Variant chr15-44668359-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3048603.Status of the report is no_assertion_criteria_provided, 0 stars.

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.1348G>A	p.Val450Met	missense	Exon 15 of 18	NP_001374192.1	C9JE40
	PATL2	NM_001145112.2		c.1348G>A	p.Val450Met	missense	Exon 13 of 16	NP_001138584.1	C9JE40
	PATL2	NM_001387261.1		c.1348G>A	p.Val450Met	missense	Exon 13 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.1348G>A	p.Val450Met	missense	Exon 15 of 18	ENSP00000508024.1	C9JE40
	PATL2	ENST00000434130.6	TSL:5	c.1348G>A	p.Val450Met	missense	Exon 13 of 16	ENSP00000416673.1	C9JE40
	PATL2	ENST00000890223.1		c.1348G>A	p.Val450Met	missense	Exon 14 of 17	ENSP00000560282.1

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000475 AC: 73 AN: 153794 AF XY: 0.000392

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000406

Gnomad ASJ exome AF: 0.00661

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.000694

GnomAD4 exome AF: 0.000188 AC: 263 AN: 1398620 Hom.: 1 Cov.: 30 AF XY: 0.000184 AC XY: 127 AN XY: 689818

African (AFR) AF: 0.0000317 AC: 1 AN: 31574

American (AMR) AF: 0.0000841 AC: 3 AN: 35680

Ashkenazi Jewish (ASJ) AF: 0.00679 AC: 171 AN: 25174

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.0000758 AC: 6 AN: 79184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49276

Middle Eastern (MID) AF: 0.000194 AC: 1 AN: 5150

European-Non Finnish (NFE) AF: 0.0000501 AC: 54 AN: 1078920

Other (OTH) AF: 0.000466 AC: 27 AN: 57924

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.000323 AC XY: 24 AN XY: 74376

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00979 AC: 34 AN: 3472

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5206

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000543 Hom.: 0

Bravo AF: 0.000249

ExAC AF: 0.000707 AC: 16

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PATL2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.95
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.0070	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.52
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.053
Sift	Benign	0.24	T
Sift4G	Benign	0.45	T
Polyphen		0.38	B
Vest4		0.093
MVP		0.061
MPC		0.00035
ClinPred		0.023	T
GERP RS		1.1
PromoterAI		-0.0099	Neutral
Varity_R		0.033
gMVP		0.073
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs760378079; hg19: chr15-44960557; COSMIC: COSV56002866; COSMIC: COSV56002866;