rs397514744

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_022114.4(PRDM16):c.872C>T(p.Pro291Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000392 in 1,606,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

PRDM16
NM_022114.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts P:1U:4

Conservation

PhyloP100: 7.66

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AD Classification: STRONG Submitted by: ClinGen
left ventricular noncompaction 8
Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
left ventricular noncompaction
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PRDM16 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.767

BS2

High AC in GnomAdExome4 at 59 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022114.4. 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
	PRDM16	NM_022114.4	MANE Select	c.872C>T	p.Pro291Leu	missense	Exon 6 of 17	NP_071397.3
	PRDM16	NM_199454.3		c.872C>T	p.Pro291Leu	missense	Exon 6 of 17	NP_955533.2	Q9HAZ2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRDM16	ENST00000270722.10	TSL:1 MANE Select	c.872C>T	p.Pro291Leu	missense	Exon 6 of 17	ENSP00000270722.5	Q9HAZ2-1
PRDM16	ENST00000378391.6	TSL:1	c.872C>T	p.Pro291Leu	missense	Exon 6 of 17	ENSP00000367643.2	Q9HAZ2-2
PRDM16	ENST00000512462.5	TSL:1	n.650C>T		non_coding_transcript_exon	Exon 5 of 16

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

149296

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000591

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000366

AC:

AN:

245952

AF XY:

0.0000298

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000634

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000405

AC:

AN:

1457266

Hom.:

Cov.:

AF XY:

0.0000414

AC XY:

AN XY:

724678

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33160

American (AMR)

AF:

0.0000448

AC:

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39612

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86038

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52038

Middle Eastern (MID)

AF:

0.000375

AC:

AN:

5336

European-Non Finnish (NFE)

AF:

0.0000477

AC:

AN:

1110158

Other (OTH)

AF:

0.0000166

AC:

AN:

60170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000268

AC:

AN:

149296

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72950

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39400

American (AMR)

AF:

0.00

AC:

AN:

15104

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4740

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10534

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000591

AC:

AN:

67630

Other (OTH)

AF:

0.00

AC:

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000453

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Left ventricular noncompaction 8 (3)

Cardiomyopathy, dilated, 1LL (1)

Primary dilated cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.085

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

M_CAP

Pathogenic

0.51

MetaRNN

Pathogenic

0.77

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

7.7

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.31

Sift

Benign

0.035

Sift4G

Uncertain

0.059

Polyphen

1.0

Vest4

0.77

MVP

0.48

MPC

1.1

ClinPred

0.93

GERP RS

4.3

Varity_R

0.34

gMVP

0.39

Mutation Taster

=52/48

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over