Variant rs765185537 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_022114.4(PRDM16):c.884+39_884+69del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00502 in 1,590,522 control chromosomes in the GnomAD database, including 280 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.026 ( 133 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 147 hom. )

Consequence

PRDM16
NM_022114.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.87

Variant links:

Genes affected

PRDM16 (HGNC:14000): (PR/SET domain 16) The reciprocal translocation t(1;3)(p36;q21) occurs in a subset of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This gene is located near the 1p36.3 breakpoint and has been shown to be specifically expressed in the t(1:3)(p36,q21)-positive MDS/AML. The protein encoded by this gene is a zinc finger transcription factor and contains an N-terminal PR domain. The translocation results in the overexpression of a truncated version of this protein that lacks the PR domain, which may play an important role in the pathogenesis of MDS and AML. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

PRDM16 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 1-3403006-GCCCTCCTCTGAGTCTTCCTCCCCTTCCCGTA-G is Benign according to our data. Variant chr1-3403006-GCCCTCCTCTGAGTCTTCCTCCCCTTCCCGTA-G is described in ClinVar as [Benign]. Clinvar id is 406244.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-3403006-GCCCTCCTCTGAGTCTTCCTCCCCTTCCCGTA-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM16	NM_022114.4 linkuse as main transcript	c.884+39_884+69del		intron_variant		ENST00000270722.10	NP_071397.3
PRDM16	NM_199454.3 linkuse as main transcript	c.884+39_884+69del		intron_variant			NP_955533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10 linkuse as main transcript	c.884+39_884+69del		intron_variant		1	NM_022114.4	ENSP00000270722	P1	Q9HAZ2-1

Frequencies

GnomAD3 genomes

AF:

0.0255

AC:

3682

AN:

144354

Hom.:

131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0928

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0133

Gnomad ASJ

AF:

0.00349

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000654

Gnomad FIN

AF:

0.000194

Gnomad MID

AF:

0.00974

Gnomad NFE

AF:

0.000946

Gnomad OTH

AF:

0.0194

GnomAD3 exomes

AF:

0.00508

AC:

1230

AN:

242072

Hom.:

AF XY:

0.00394

AC XY:

522

AN XY:

132530

show subpopulations

Gnomad AFR exome

AF:

0.0639

Gnomad AMR exome

AF:

0.00470

Gnomad ASJ exome

AF:

0.00233

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000165

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.000915

Gnomad OTH exome

AF:

0.00505

GnomAD4 exome

AF:

0.00296

AC:

4286

AN:

1446052

Hom.:

147

AF XY:

0.00266

AC XY:

1912

AN XY:

718496

show subpopulations

Gnomad4 AFR exome

AF:

0.0834

Gnomad4 AMR exome

AF:

0.00713

Gnomad4 ASJ exome

AF:

0.00269

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000503

Gnomad4 FIN exome

AF:

0.000193

Gnomad4 NFE exome

AF:

0.000669

Gnomad4 OTH exome

AF:

0.00679

GnomAD4 genome

AF:

0.0255

AC:

3691

AN:

144470

Hom.:

133

Cov.:

AF XY:

0.0249

AC XY:

1763

AN XY:

70708

show subpopulations

Gnomad4 AFR

AF:

0.0927

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.00349

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000654

Gnomad4 FIN

AF:

0.000194

Gnomad4 NFE

AF:

0.000946

Gnomad4 OTH

AF:

0.0192

Alfa

AF:

0.0113

Hom.:

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jun 05, 2015

c.884+39_884+69del in intron 6 of PRDM16: This variant is not expected to have c linical significance because it has been identified at a frequency of 22.4% (192 18/85718 chromosomes) across all populations by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs148238606). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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