chr1-3412095-C-T

Position:

chr1-3412095-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022114.4(PRDM16):c.1898C>T(p.Pro633Leu) variant causes a missense change. The variant allele was found at a frequency of 0.135 in 1,586,060 control chromosomes in the GnomAD database, including 15,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1614 hom., cov: 33)

Exomes 𝑓: 0.13 ( 14027 hom. )

Consequence

PRDM16
NM_022114.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 4.65

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:

PRDM16 (HGNC:):

PRDM16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017106235).

BP6

Variant 1-3412095-C-T is Benign according to our data. Variant chr1-3412095-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 227027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-3412095-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 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.1898C>T	p.Pro633Leu	missense_variant	9/17	ENST00000270722.10	NP_071397.3	Q9HAZ2-1
PRDM16	NM_199454.3 linkuse as main transcript	c.1898C>T	p.Pro633Leu	missense_variant	9/17		NP_955533.2	Q9HAZ2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10 linkuse as main transcript	c.1898C>T	p.Pro633Leu	missense_variant	9/17	1	NM_022114.4	ENSP00000270722.5		Q9HAZ2-1

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21321

AN:

151990

Hom.:

1612

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.0965

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.214

Gnomad EAS

AF:

0.00931

Gnomad SAS

AF:

0.0720

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.158

GnomAD3 exomes

AF:

0.123

AC:

28161

AN:

228982

Hom.:

2098

AF XY:

0.125

AC XY:

15454

AN XY:

123872

show subpopulations

Gnomad AFR exome

AF:

0.164

Gnomad AMR exome

AF:

0.0802

Gnomad ASJ exome

AF:

0.223

Gnomad EAS exome

AF:

0.0108

Gnomad SAS exome

AF:

0.0762

Gnomad FIN exome

AF:

0.0988

Gnomad NFE exome

AF:

0.156

Gnomad OTH exome

AF:

0.154

GnomAD4 exome

AF:

0.135

AC:

193548

AN:

1433952

Hom.:

14027

Cov.:

AF XY:

0.134

AC XY:

95216

AN XY:

709876

show subpopulations

Gnomad4 AFR exome

AF:

0.161

Gnomad4 AMR exome

AF:

0.0849

Gnomad4 ASJ exome

AF:

0.215

Gnomad4 EAS exome

AF:

0.00691

Gnomad4 SAS exome

AF:

0.0774

Gnomad4 FIN exome

AF:

0.106

Gnomad4 NFE exome

AF:

0.144

Gnomad4 OTH exome

AF:

0.139

GnomAD4 genome

AF:

0.140

AC:

21323

AN:

152108

Hom.:

1614

Cov.:

AF XY:

0.136

AC XY:

10139

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.163

Gnomad4 AMR

AF:

0.115

Gnomad4 ASJ

AF:

0.214

Gnomad4 EAS

AF:

0.00933

Gnomad4 SAS

AF:

0.0715

Gnomad4 FIN

AF:

0.102

Gnomad4 NFE

AF:

0.148

Gnomad4 OTH

AF:

0.158

Alfa

AF:

0.151

Hom.:

4449

Bravo

AF:

0.143

TwinsUK

AF:

0.139

AC:

516

ALSPAC

AF:

0.145

AC:

558

ESP6500AA

AF:

0.154

AC:

659

ESP6500EA

AF:

0.152

AC:

1283

ExAC

AF:

0.126

AC:

15289

Asia WGS

AF:

0.0560

AC:

195

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Pro633Leu in exon 9 of PRDM16: This variant is not expected to have clinical sig nificance because it has been identified in 15.4% (659/4286) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs2493292). -
Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 10, 2023	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 23, 2016	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, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Left ventricular noncompaction 8

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0055

T;.;.;T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.037

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

D;D;D;D;D

MetaRNN

Benign

0.0017

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.69

.;N;.;N;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.23

N;N;N;N;N

REVEL

Benign

0.074

Sift

Uncertain

0.023

D;D;D;D;D

Sift4G

Benign

0.33

T;T;T;T;T

Polyphen

0.066, 0.039

.;B;.;B;.

Vest4

0.076

MPC

0.37

ClinPred

0.016

GERP RS

4.2

Varity_R

0.047

gMVP

0.11

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