rs199614349

Positions:

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_022114.4(PRDM16):c.201G>A(p.Pro67=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,611,576 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 14 hom. )

Consequence

PRDM16
NM_022114.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.823

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 1-3186288-G-A is Benign according to our data. Variant chr1-3186288-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-3186288-G-A is described in Lovd as [Benign]. Variant chr1-3186288-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.823 with no splicing effect.

BS2

High AC in GnomAd4 at 246 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM16	NM_022114.4 linkuse as main transcript	c.201G>A	p.Pro67=	synonymous_variant	2/17	ENST00000270722.10	NP_071397.3
PRDM16	NM_199454.3 linkuse as main transcript	c.201G>A	p.Pro67=	synonymous_variant	2/17		NP_955533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10 linkuse as main transcript	c.201G>A	p.Pro67=	synonymous_variant	2/17	1	NM_022114.4	ENSP00000270722	P1	Q9HAZ2-1

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

246

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00184

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00225

AC:

552

AN:

245588

Hom.:

AF XY:

0.00244

AC XY:

326

AN XY:

133878

show subpopulations

Gnomad AFR exome

AF:

0.000391

Gnomad AMR exome

AF:

0.00137

Gnomad ASJ exome

AF:

0.0203

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00131

Gnomad FIN exome

AF:

0.000233

Gnomad NFE exome

AF:

0.00210

Gnomad OTH exome

AF:

0.00351

GnomAD4 exome

AF:

0.00173

AC:

2521

AN:

1459290

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

1302

AN XY:

725834

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.00150

Gnomad4 ASJ exome

AF:

0.0193

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00132

Gnomad4 FIN exome

AF:

0.000250

Gnomad4 NFE exome

AF:

0.00140

Gnomad4 OTH exome

AF:

0.00307

GnomAD4 genome

AF:

0.00162

AC:

246

AN:

152286

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

126

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.0199

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00184

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00290

Hom.:

Bravo

AF:

0.00159

EpiCase

AF:

0.00278

EpiControl

AF:

0.00314

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 27, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 17, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	p.Pro67Pro in exon 2 of PRDM16: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 0.3% (212/64514) o f European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs199614349). -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Left ventricular noncompaction 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

8.9

DANN

Benign

0.70

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