chr11-59655712-T-G

Position:

• chr11-59655712-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152716.3(PATL1):​c.842A>C​(p.Gln281Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000207 in 1,447,858 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: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PATL1 NM_152716.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.85

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.744

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PATL1	NM_152716.3	c.842A>C	p.Gln281Pro	missense_variant	8/19	ENST00000300146.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PATL1	ENST00000300146.10	c.842A>C	p.Gln281Pro	missense_variant	8/19	1	NM_152716.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1447858 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 718760

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The c.842A>C (p.Q281P) alteration is located in exon 8 (coding exon 8) of the PATL1 gene. This alteration results from a A to C substitution at nucleotide position 842, causing the glutamine (Q) at amino acid position 281 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0068	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.014	T
MetaRNN	Pathogenic	0.74	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	0.41	N
REVEL	Benign	0.23
Sift	Benign	0.31	T
Sift4G	Benign	0.27	T
Polyphen		1.0	D
Vest4		0.76
MutPred		0.66		Gain of loop (P = 0.024);
MVP		0.37
MPC		1.0
ClinPred		0.83	D
GERP RS		4.9
Varity_R		0.12
gMVP		0.39

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-59423185;