4-20709767-A-G

Variant names:

• chr4-20709767-A-G
• rs372255889
• NM_001258345.3:c.360A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP7

The NM_001258345.3(PACRGL):​c.360A>G​(p.Leu120Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000276 in 1,591,076 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.

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (0 hom.)
• Consequence: PACRGL NM_001258345.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597
• Publications: 0 publications found

Genes affected

PACRGL (HGNC:28442): (parkin coregulated like)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.061).
• BP7: Synonymous conserved (PhyloP=0.597 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258345.3. 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
	PACRGL	NM_001258345.3	MANE Select	c.360A>G	p.Leu120Leu	synonymous	Exon 5 of 9	NP_001245274.1	Q8N7B6-1
	PACRGL	NM_145048.5		c.360A>G	p.Leu120Leu	synonymous	Exon 5 of 8	NP_659485.1	Q8N7B6-2
	PACRGL	NM_001258346.3		c.208-3021A>G		intron	N/A	NP_001245275.1	Q8N7B6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PACRGL	ENST00000503585.6	TSL:2 MANE Select	c.360A>G	p.Leu120Leu	synonymous	Exon 5 of 9	ENSP00000423881.1	Q8N7B6-1
	PACRGL	ENST00000510051.5	TSL:1	c.504A>G	p.Leu168Leu	synonymous	Exon 7 of 9	ENSP00000423499.1	D6R9N9
	PACRGL	ENST00000360916.9	TSL:1	c.360A>G	p.Leu120Leu	synonymous	Exon 5 of 8	ENSP00000354171.4	Q8N7B6-2

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

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: 0.000338

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000104 AC: 26 AN: 249916 AF XY: 0.000118

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000212

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000287 AC: 413 AN: 1438900 Hom.: 0 Cov.: 28 AF XY: 0.000284 AC XY: 204 AN XY: 717096

African (AFR) AF: 0.0000608 AC: 2 AN: 32916

American (AMR) AF: 0.00 AC: 0 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.00 AC: 0 AN: 39438

South Asian (SAS) AF: 0.00 AC: 0 AN: 85538

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 0.000368 AC: 402 AN: 1092088

Other (OTH) AF: 0.000151 AC: 9 AN: 59626

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74350

African (AFR) AF: 0.0000724 AC: 3 AN: 41452

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

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000182 Hom.: 0

Bravo AF: 0.000204

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.6
DANN	Benign	0.80
PhyloP100		0.60

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

Other links and lift over

dbSNP: rs372255889; hg19: chr4-20711390;