Genetic Variant PRDM16:c.38-18977T>C (chr1-3167148-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022114.4(PRDM16):c.38-18977T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,860 control chromosomes in the GnomAD database, including 20,851 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.51 ( 20851 hom., cov: 33)

Consequence

PRDM16
NM_022114.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.74

Publications

77 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:

ENSG00000306427 (HGNC:):

ENSG00000306427 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM16	NM_022114.4 link	c.38-18977T>C		intron_variant	Intron 1 of 16	ENST00000270722.10	NP_071397.3
PRDM16	NM_199454.3 link	c.38-18977T>C		intron_variant	Intron 1 of 16		NP_955533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10 link	c.38-18977T>C		intron_variant	Intron 1 of 16	1	NM_022114.4	ENSP00000270722.5

Frequencies

GnomAD3 genomes

AF:

0.510

AC:

77436

AN:

151744

Hom.:

20835

Cov.:

show subpopulations

Gnomad AFR

AF:

0.693

Gnomad AMI

AF:

0.495

Gnomad AMR

AF:

0.515

Gnomad ASJ

AF:

0.435

Gnomad EAS

AF:

0.411

Gnomad SAS

AF:

0.500

Gnomad FIN

AF:

0.368

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.433

Gnomad OTH

AF:

0.511

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.510

AC:

77491

AN:

151860

Hom.:

20851

Cov.:

AF XY:

0.510

AC XY:

37818

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.692

AC:

28682

AN:

41422

American (AMR)

AF:

0.515

AC:

7861

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.435

AC:

1510

AN:

3472

East Asian (EAS)

AF:

0.410

AC:

2103

AN:

5132

South Asian (SAS)

AF:

0.500

AC:

2407

AN:

4816

European-Finnish (FIN)

AF:

0.368

AC:

3877

AN:

10544

Middle Eastern (MID)

AF:

0.421

AC:

123

AN:

292

European-Non Finnish (NFE)

AF:

0.433

AC:

29399

AN:

67892

Other (OTH)

AF:

0.512

AC:

1079

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

1892

3784

5675

7567

9459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

676

1352

2028

2704

3380

<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:

0.458

Hom.:

63188

Bravo

AF:

0.526

Asia WGS

AF:

0.433

AC:

1502

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.014

(source)

DANN

Benign

0.31

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over