Variant rs188634763 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_022114.4(PRDM16):c.3687T>C(p.Ala1229Ala) variant causes a synonymous change. The variant allele was found at a frequency of 0.000278 in 1,613,288 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 2 hom. )

Consequence

PRDM16
NM_022114.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.74

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 1-3432131-T-C is Benign according to our data. Variant chr1-3432131-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 227037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-3432131-T-C is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 202 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM16	NM_022114.4 linkuse as main transcript	c.3687T>C	p.Ala1229Ala	synonymous_variant	16/17	ENST00000270722.10	NP_071397.3	Q9HAZ2-1
PRDM16	NM_199454.3 linkuse as main transcript	c.3687T>C	p.Ala1229Ala	synonymous_variant	16/17		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.3687T>C	p.Ala1229Ala	synonymous_variant	16/17	1	NM_022114.4	ENSP00000270722.5		Q9HAZ2-1

Frequencies

GnomAD3 genomes

AF:

0.00132

AC:

201

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00432

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000428

AC:

106

AN:

247656

Hom.:

AF XY:

0.000297

AC XY:

AN XY:

134524

show subpopulations

Gnomad AFR exome

AF:

0.00572

Gnomad AMR exome

AF:

0.000378

Gnomad ASJ exome

AF:

0.000400

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000894

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000169

AC:

247

AN:

1461028

Hom.:

Cov.:

AF XY:

0.000143

AC XY:

104

AN XY:

726794

show subpopulations

Gnomad4 AFR exome

AF:

0.00523

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.000460

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000596

GnomAD4 genome

AF:

0.00133

AC:

202

AN:

152260

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00433

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000752

Hom.:

Bravo

AF:

0.00152

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 08, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 24, 2014

Ala1229Ala in exon 16 of PRDM16: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 0.6% (22/3884) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs188634763). -

Left ventricular noncompaction 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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