1-3186339-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_022114.4(PRDM16):c.252C>T(p.Phe84Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000515 in 1,612,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

PRDM16
NM_022114.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.63

Publications

1 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):

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

PRDM16 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 1-3186339-C-T is Benign according to our data. Variant chr1-3186339-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 504756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.63 with no splicing effect.

BS2

High AC in GnomAd4 at 29 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM16	NM_022114.4 link	c.252C>T	p.Phe84Phe	synonymous_variant	Exon 2 of 17	ENST00000270722.10	NP_071397.3
PRDM16	NM_199454.3 link	c.252C>T	p.Phe84Phe	synonymous_variant	Exon 2 of 17		NP_955533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10 link	c.252C>T	p.Phe84Phe	synonymous_variant	Exon 2 of 17	1	NM_022114.4	ENSP00000270722.5

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000735

AC:

AN:

244862

AF XY:

0.0000299

show subpopulations

Gnomad AFR exome

AF:

0.000328

Gnomad AMR exome

AF:

0.0000872

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000391

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000274

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000370

AC:

AN:

1460076

Hom.:

Cov.:

AF XY:

0.0000317

AC XY:

AN XY:

726256

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33476

American (AMR)

AF:

0.0000672

AC:

AN:

44664

Ashkenazi Jewish (ASJ)

AF:

0.000153

AC:

AN:

26114

East Asian (EAS)

AF:

0.000202

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86138

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52124

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000225

AC:

AN:

1111742

Other (OTH)

AF:

0.0000331

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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:

0.000190

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

41570

American (AMR)

AF:

0.0000654

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.000582

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68028

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.0000450

Hom.:

Bravo

AF:

0.000159

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Phe84Phe 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 9/23790 of African chromosomes by the Genome Aggregation Database (gnomAD; http://gnomad.broadinst itute.org/; dbSNP rs370290776). -

May 18, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Sep 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PRDM16: BP4, BP7 -

Jun 10, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Left ventricular noncompaction 8

Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.4

(source)

DANN

Benign

0.58

PhyloP100

1.6

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over