ENST00000563500.5:c.*608T>G

Variant names:

• chr15-74034216-T-G
• rs2304717
• ENST00000563500.5:c.*608T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000563500.5(PML):​c.*608T>G variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PML ENST00000563500.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.590
• Publications: 5 publications found

Genes affected

PML (HGNC:9113): (PML nuclear body scaffold) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This phosphoprotein localizes to nuclear bodies where it functions as a transcription factor and tumor suppressor. Its expression is cell-cycle related and it regulates the p53 response to oncogenic signals. The gene is often involved in the translocation with the retinoic acid receptor alpha gene associated with acute promyelocytic leukemia (APL). Extensive alternative splicing of this gene results in several variations of the protein's central and C-terminal regions; all variants encode the same N-terminus. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000563500.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PML	NM_033238.3	MANE Select	c.1658-262T>G		intron	N/A	NP_150241.2
	PML	NM_033239.3		c.1658-262T>G		intron	N/A	NP_150242.1
	PML	NM_033250.3		c.1514-262T>G		intron	N/A	NP_150253.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PML	ENST00000563500.5	TSL:1	c.*608T>G		3_prime_UTR	Exon 5 of 5	ENSP00000457032.1
	PML	ENST00000268058.8	TSL:1 MANE Select	c.1658-262T>G		intron	N/A	ENSP00000268058.3
	PML	ENST00000565898.5	TSL:1	c.1514-262T>G		intron	N/A	ENSP00000455838.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 388390 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 205100

African (AFR) AF: 0.00 AC: 0 AN: 11428

American (AMR) AF: 0.00 AC: 0 AN: 19476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12192

East Asian (EAS) AF: 0.00 AC: 0 AN: 24996

South Asian (SAS) AF: 0.00 AC: 0 AN: 45718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1630

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 228852

Other (OTH) AF: 0.00 AC: 0 AN: 22182

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.71
DANN	Benign	0.56
PhyloP100		-0.59

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: rs2304717; hg19: chr15-74326557;