chr11-59639081-C-A

Variant names:

• chr11-59639081-C-A
• rs1332685778
• NM_152716.3:c.2258G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152716.3(PATL1):​c.2258G>T​(p.Arg753Leu) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R753Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PATL1 NM_152716.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.984
• Publications: 0 publications found

Genes affected

PATL1 (HGNC:26721): (PAT1 homolog 1, processing body mRNA decay factor) Enables poly(G) binding activity and poly(U) RNA binding activity. Involved in P-body assembly and deadenylation-dependent decapping of nuclear-transcribed mRNA. Located in P-body and cytosol. Colocalizes with CCR4-NOT complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000255139 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17917895).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152716.3. 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
	PATL1	NM_152716.3	MANE Select	c.2258G>T	p.Arg753Leu	missense	Exon 18 of 19	NP_689929.2	Q86TB9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PATL1	ENST00000300146.10	TSL:1 MANE Select	c.2258G>T	p.Arg753Leu	missense	Exon 18 of 19	ENSP00000300146.9	Q86TB9-1
	PATL1	ENST00000940124.1		c.2252G>T	p.Arg751Leu	missense	Exon 18 of 19	ENSP00000610183.1
	PATL1	ENST00000940125.1		c.2210G>T	p.Arg737Leu	missense	Exon 18 of 19	ENSP00000610184.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.98
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.18
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.062	T
Polyphen		0.11	B
Vest4		0.47
MutPred		0.45		Loss of MoRF binding (P = 0.0295)
MVP		0.16
MPC		0.35
ClinPred		0.86	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.52
gMVP		0.38
Mutation Taster		=62/38	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1332685778; hg19: chr11-59406554;