chr11-59650791-C-A

Variant names:

• chr11-59650791-C-A
• rs763444872
• NM_152716.3:c.1547G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152716.3(PATL1):​c.1547G>T​(p.Arg516Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000257 in 1,556,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R516Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PATL1 NM_152716.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.77
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30889267).

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.1547G>T	p.Arg516Leu	missense	Exon 13 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.1547G>T	p.Arg516Leu	missense	Exon 13 of 19	ENSP00000300146.9	Q86TB9-1
	PATL1	ENST00000940124.1		c.1541G>T	p.Arg514Leu	missense	Exon 13 of 19	ENSP00000610183.1
	PATL1	ENST00000940125.1		c.1499G>T	p.Arg500Leu	missense	Exon 13 of 19	ENSP00000610184.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1404596 Hom.: 0 Cov.: 28 AF XY: 0.00000144 AC XY: 1 AN XY: 693840

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000309 AC: 1 AN: 32374

American (AMR) AF: 0.00 AC: 0 AN: 35766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25292

East Asian (EAS) AF: 0.00 AC: 0 AN: 37712

South Asian (SAS) AF: 0.00 AC: 0 AN: 79310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080740

Other (OTH) AF: 0.00 AC: 0 AN: 58182

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152220 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74366

African (AFR) AF: 0.0000723 AC: 3 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15270

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

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: 0.00 AC: 0 AN: 68036

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
Eigen	Uncertain	0.63
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.8
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.19
Sift	Benign	0.27	T
Sift4G	Benign	0.23	T
Polyphen		0.99	D
Vest4		0.37
MutPred		0.56		Loss of MoRF binding (P = 0.017)
MVP		0.15
MPC		0.58
ClinPred		0.92	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.26
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs763444872; hg19: chr11-59418264;