rs1052242

Positions:

• chr15-74028137-T-C
• chr15-74028137-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033238.3(PML):​c.1254+3210T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 152,098 control chromosomes in the GnomAD database, including 23,302 homozygotes. 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 0.55 (23301 hom., cov: 33)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: PML NM_033238.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344

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]

PML (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PML	NM_033238.3	c.1254+3210T>C		intron_variant		ENST00000268058.8	NP_150241.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PML	ENST00000268058.8	c.1254+3210T>C		intron_variant		1	NM_033238.3	ENSP00000268058.3

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83704 AN: 151972 Hom.: 23298 Cov.: 33

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.548

GnomAD4 exome AF: 0.500 AC: 5 AN: 10 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 4 AN XY: 8

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.333

GnomAD4 genome AF: 0.551 AC: 83748 AN: 152088 Hom.: 23301 Cov.: 33 AF XY: 0.555 AC XY: 41248 AN XY: 74374

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.635

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.550

Alfa AF: 0.574 Hom.: 11381

Bravo AF: 0.537

Asia WGS AF: 0.605 AC: 2100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.72

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: rs1052242; hg19: chr15-74320478;