15-44666454-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001387263.1(PATL2):c.1551A>G(p.Leu517=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,551,638 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0089 (15 hom., cov: 32)
  • Exomes 𝑓: 0.00081 (14 hom.)
• Consequence: PATL2 NM_001387263.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.446

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021742284).
• BP6: Variant 15-44666454-T-C is Benign according to our data. Variant chr15-44666454-T-C is described in ClinVar as [Benign]. Clinvar id is 774222.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.446 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00885 (1348/152252) while in subpopulation AFR AF= 0.0312 (1296/41544). AF 95% confidence interval is 0.0298. There are 15 homozygotes in gnomad4. There are 620 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PATL2	NM_001387263.1	c.1551A>G	p.Leu517=	synonymous_variant	17/18	ENST00000682850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PATL2	ENST00000682850.1	c.1551A>G	p.Leu517=	synonymous_variant	17/18		NM_001387263.1	A2

Frequencies

GnomAD3 genomes AF: 0.00888 AC: 1351 AN: 152134 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00210 AC: 323 AN: 154050 Hom.: 6 AF XY: 0.00166 AC XY: 136 AN XY: 81742

Gnomad AFR exome AF: 0.0351

Gnomad AMR exome AF: 0.00162

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000670

Gnomad OTH exome AF: 0.000231

GnomAD4 exome AF: 0.000814 AC: 1139 AN: 1399386 Hom.: 14 Cov.: 31 AF XY: 0.000711 AC XY: 491 AN XY: 690206

Gnomad4 AFR exome AF: 0.0299

Gnomad4 AMR exome AF: 0.00168

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000379

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000222

Gnomad4 OTH exome AF: 0.00178

GnomAD4 genome AF: 0.00885 AC: 1348 AN: 152252 Hom.: 15 Cov.: 32 AF XY: 0.00833 AC XY: 620 AN XY: 74440

Gnomad4 AFR AF: 0.0312

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00435 Hom.: 2

Bravo AF: 0.00971

ESP6500AA AF: 0.0269 AC: 37

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00305 AC: 69

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 06, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	4.2
Dann	Benign	0.73
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.0022	T
MutationTaster	Benign	1.0	D;D;D
PROVEAN	Benign	-0.52	N
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
MVP		0.16
GERP RS		-7.5

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

LitVar

Other links and lift over

dbSNP: rs1044545; hg19: chr15-44958652;