chr1-3385157-C-T

Position:

chr1-3385157-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022114.4(PRDM16):c.444C>T(p.Ser148=) 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

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 -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 id is 227041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-3385157-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
PRDM16	NM_022114.4 linkuse as main transcript	c.444C>T	p.Ser148=	synonymous_variant	4/17	ENST00000270722.10	NP_071397.3
PRDM16	NM_199454.3 linkuse as main transcript	c.444C>T	p.Ser148=	synonymous_variant	4/17		NP_955533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10 linkuse as main transcript	c.444C>T	p.Ser148=	synonymous_variant	4/17	1	NM_022114.4	ENSP00000270722	P1	Q9HAZ2-1

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

GnomAD3 exomes

AF:

0.334

AC:

83041

AN:

248906

Hom.:

16086

AF XY:

0.342

AC XY:

46254

AN XY:

135264

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 SAS exome

AF:

0.523

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

Gnomad4 AFR exome

AF:

0.0722

Gnomad4 AMR exome

AF:

0.390

Gnomad4 ASJ exome

AF:

0.217

Gnomad4 EAS exome

AF:

0.588

Gnomad4 SAS exome

AF:

0.520

Gnomad4 FIN exome

AF:

0.303

Gnomad4 NFE exome

AF:

0.271

Gnomad4 OTH exome

AF:

0.300

GnomAD4 genome

AF:

0.246

AC:

37368

AN:

152106

Hom.:

5872

Cov.:

AF XY:

0.257

AC XY:

19114

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0795

Gnomad4 AMR

AF:

0.335

Gnomad4 ASJ

AF:

0.214

Gnomad4 EAS

AF:

0.604

Gnomad4 SAS

AF:

0.528

Gnomad4 FIN

AF:

0.307

Gnomad4 NFE

AF:

0.271

Gnomad4 OTH

AF:

0.246

Alfa

AF:

0.257

Hom.:

3816

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

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 DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 09, 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, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	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). -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 04, 2023	- -

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

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.90

DANN

Benign

0.60

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

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