1-3385157-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022114.4(PRDM16):c.444C>T(p.Ser148Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,613,150 control chromosomes in the GnomAD database, including 75,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5872 hom., cov: 33)

Exomes 𝑓: 0.29 ( 69832 hom. )

Consequence

PRDM16
NM_022114.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.79

Publications

18 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 1-3385157-C-T is Benign according to our data. Variant chr1-3385157-C-T is described in ClinVar as Benign. ClinVar VariationId is 227041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.79 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM16	NM_022114.4 link	c.444C>T	p.Ser148Ser	synonymous_variant	Exon 4 of 17	ENST00000270722.10	NP_071397.3
PRDM16	NM_199454.3 link	c.444C>T	p.Ser148Ser	synonymous_variant	Exon 4 of 17		NP_955533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10 link	c.444C>T	p.Ser148Ser	synonymous_variant	Exon 4 of 17	1	NM_022114.4	ENSP00000270722.5

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37367

AN:

151988

Hom.:

5880

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0797

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.335

Gnomad ASJ

AF:

0.214

Gnomad EAS

AF:

0.604

Gnomad SAS

AF:

0.527

Gnomad FIN

AF:

0.307

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.247

GnomAD2 exomes

AF:

0.334

AC:

83041

AN:

248906

AF XY:

0.342

show subpopulations

Gnomad AFR exome

AF:

0.0766

Gnomad AMR exome

AF:

0.404

Gnomad ASJ exome

AF:

0.210

Gnomad EAS exome

AF:

0.599

Gnomad FIN exome

AF:

0.307

Gnomad NFE exome

AF:

0.271

Gnomad OTH exome

AF:

0.302

GnomAD4 exome

AF:

0.295

AC:

430644

AN:

1461044

Hom.:

69832

Cov.:

AF XY:

0.302

AC XY:

219240

AN XY:

726810

show subpopulations

African (AFR)

AF:

0.0722

AC:

2416

AN:

33478

American (AMR)

AF:

0.390

AC:

17445

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

5680

AN:

26136

East Asian (EAS)

AF:

0.588

AC:

23336

AN:

39700

South Asian (SAS)

AF:

0.520

AC:

44829

AN:

86252

European-Finnish (FIN)

AF:

0.303

AC:

15969

AN:

52764

Middle Eastern (MID)

AF:

0.312

AC:

1795

AN:

5750

European-Non Finnish (NFE)

AF:

0.271

AC:

301054

AN:

1111866

Other (OTH)

AF:

0.300

AC:

18120

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

15719

31438

47156

62875

78594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10360

20720

31080

41440

51800

<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:

0.246

AC:

37368

AN:

152106

Hom.:

5872

Cov.:

AF XY:

0.257

AC XY:

19114

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.0795

AC:

3304

AN:

41538

American (AMR)

AF:

0.335

AC:

5119

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

743

AN:

3470

East Asian (EAS)

AF:

0.604

AC:

3103

AN:

5140

South Asian (SAS)

AF:

0.528

AC:

2541

AN:

4816

European-Finnish (FIN)

AF:

0.307

AC:

3249

AN:

10568

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.271

AC:

18432

AN:

67976

Other (OTH)

AF:

0.246

AC:

519

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1364

2727

4091

5454

6818

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

388

776

1164

1552

1940

<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:

0.254

Hom.:

4871

Bravo

AF:

0.236

Asia WGS

AF:

0.520

AC:

1806

AN:

3478

EpiCase

AF:

0.262

EpiControl

AF:

0.269

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Ser148Ser in exon 4 of PRDM16: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 26.7% (2281/8548) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2282198). -

Apr 04, 2023

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 09, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Left ventricular noncompaction 8

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.90

(source)

DANN

Benign

0.60

PhyloP100

-2.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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