Genetic Variant PRDM16:c.884+39_884+69dupACCCTCCTCTGAGTCTTCCTCCCCTTCCCGT (chr1-3403006-G-GCCCTCCTCTGAGTCTTCCTCCCCTTCCCGTA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_022114.4(PRDM16):c.884+39_884+69dupACCCTCCTCTGAGTCTTCCTCCCCTTCCCGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 144,520 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRDM16
NM_022114.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.373

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM16	NM_022114.4 link	c.884+39_884+69dupACCCTCCTCTGAGTCTTCCTCCCCTTCCCGT		intron_variant	Intron 6 of 16	ENST00000270722.10	NP_071397.3
PRDM16	NM_199454.3 link	c.884+39_884+69dupACCCTCCTCTGAGTCTTCCTCCCCTTCCCGT		intron_variant	Intron 6 of 16		NP_955533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10 link	c.884+8_884+9insCCCTCCTCTGAGTCTTCCTCCCCTTCCCGTA		intron_variant	Intron 6 of 16	1	NM_022114.4	ENSP00000270722.5

Frequencies

GnomAD3 genomes

AF:

0.0000138

AC:

AN:

144406

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000393

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000484

AC:

AN:

1446188

Hom.:

Cov.:

AF XY:

0.00000557

AC XY:

AN XY:

718546

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31994

American (AMR)

AF:

0.00

AC:

AN:

44468

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26010

East Asian (EAS)

AF:

0.000152

AC:

AN:

39374

South Asian (SAS)

AF:

0.00

AC:

AN:

85534

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51742

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4638

European-Non Finnish (NFE)

AF:

9.07e-7

AC:

AN:

1102918

Other (OTH)

AF:

0.00

AC:

AN:

59510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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:

0.0000138

AC:

AN:

144520

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

70734

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

36406

American (AMR)

AF:

0.00

AC:

AN:

14860

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3442

East Asian (EAS)

AF:

0.000393

AC:

AN:

5084

South Asian (SAS)

AF:

0.00

AC:

AN:

4586

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66582

Other (OTH)

AF:

0.00

AC:

AN:

2034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.37

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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1-3403006-GCCCTCCTCTGAGTCTTCCTCCCCTTCCCGTA-GCCCTCCTCTGAGTCTTCCTCCCCTTCCCGTACCCTCCTCTGAGTCTTCCTCCCCTTCCCGTA

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