chr15-74046121-C-T

Variant names:

• chr15-74046121-C-T
• rs1036673
• NM_033238.3:c.*1113C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033238.3(PML):​c.*1113C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 232,768 control chromosomes in the GnomAD database, including 54,737 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 0.66 (33620 hom., cov: 32)
  • Exomes 𝑓: 0.72 (21117 hom.)
• Consequence: PML NM_033238.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13
• Publications: 14 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033238.3. 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
	PML	NM_033238.3	MANE Select	c.*1113C>T		3_prime_UTR	Exon 9 of 9	NP_150241.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PML	ENST00000268058.8	TSL:1 MANE Select	c.*1113C>T		3_prime_UTR	Exon 9 of 9	ENSP00000268058.3
	PML	ENST00000565898.5	TSL:1	c.*1113C>T		3_prime_UTR	Exon 8 of 8	ENSP00000455838.1
	PML	ENST00000868523.1		c.*1113C>T		3_prime_UTR	Exon 9 of 9	ENSP00000538582.1

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99544 AN: 151944 Hom.: 33595 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.684

GnomAD4 exome AF: 0.721 AC: 58153 AN: 80706 Hom.: 21117 Cov.: 0 AF XY: 0.721 AC XY: 26776 AN XY: 37116

African (AFR) AF: 0.495 AC: 1924 AN: 3888

American (AMR) AF: 0.810 AC: 2010 AN: 2482

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 3931 AN: 5106

East Asian (EAS) AF: 0.673 AC: 7642 AN: 11356

South Asian (SAS) AF: 0.764 AC: 538 AN: 704

European-Finnish (FIN) AF: 0.613 AC: 38 AN: 62

Middle Eastern (MID) AF: 0.820 AC: 402 AN: 490

European-Non Finnish (NFE) AF: 0.740 AC: 36892 AN: 49878

Other (OTH) AF: 0.709 AC: 4776 AN: 6740

GnomAD4 genome AF: 0.655 AC: 99613 AN: 152062 Hom.: 33620 Cov.: 32 AF XY: 0.657 AC XY: 48838 AN XY: 74338

African (AFR) AF: 0.482 AC: 19961 AN: 41442

American (AMR) AF: 0.777 AC: 11877 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 2733 AN: 3472

East Asian (EAS) AF: 0.638 AC: 3290 AN: 5160

South Asian (SAS) AF: 0.773 AC: 3728 AN: 4824

European-Finnish (FIN) AF: 0.628 AC: 6643 AN: 10574

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.722 AC: 49064 AN: 67988

Other (OTH) AF: 0.687 AC: 1454 AN: 2116

Alfa AF: 0.718 Hom.: 72378

Bravo AF: 0.660

Asia WGS AF: 0.682 AC: 2374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.40
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs1036673; hg19: chr15-74338462;