Variant chr15-74023017-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_033238.3(PML):c.792C>T(p.Ala264=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00703 in 1,607,302 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0072 ( 54 hom. )

Consequence

PML
NM_033238.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.82

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 15-74023017-C-T is Benign according to our data. Variant chr15-74023017-C-T is described in ClinVar as [Benign]. Clinvar id is 774496.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.82 with no splicing effect.

BS2

High AC in GnomAd4 at 751 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PML	NM_033238.3 linkuse as main transcript	c.792C>T	p.Ala264=	synonymous_variant	3/9	ENST00000268058.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PML	ENST00000268058.8 linkuse as main transcript	c.792C>T	p.Ala264=	synonymous_variant	3/9	1	NM_033238.3	P1	P29590-1

Frequencies

GnomAD3 genomes

AF:

0.00493

AC:

751

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00746

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00763

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00428

AC:

983

AN:

229808

Hom.:

AF XY:

0.00413

AC XY:

523

AN XY:

126706

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00260

Gnomad ASJ exome

AF:

0.00374

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000992

Gnomad FIN exome

AF:

0.00245

Gnomad NFE exome

AF:

0.00759

Gnomad OTH exome

AF:

0.00382

GnomAD4 exome

AF:

0.00725

AC:

10542

AN:

1454968

Hom.:

Cov.:

AF XY:

0.00702

AC XY:

5085

AN XY:

723868

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.00252

Gnomad4 ASJ exome

AF:

0.00323

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000930

Gnomad4 FIN exome

AF:

0.00308

Gnomad4 NFE exome

AF:

0.00880

Gnomad4 OTH exome

AF:

0.00613

GnomAD4 genome

AF:

0.00493

AC:

751

AN:

152334

Hom.:

Cov.:

AF XY:

0.00476

AC XY:

355

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00745

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00377

Gnomad4 NFE

AF:

0.00763

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00629

Hom.:

Bravo

AF:

0.00497

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

5.8

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over