Genetic Variant PRDM16:c.-14C>T (chr1-3069246-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_022114.4(PRDM16):c.-14C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 1,573,200 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00010 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

PRDM16
NM_022114.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.45

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 links:

PRDM16-DT (HGNC:48664): (PRDM16 divergent transcript)

PRDM16-DT links:

LOC124903827 (HGNC:):

LOC124903827 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BS2

High AC in GnomAd4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM16	NM_022114.4 link	c.-14C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 17	ENST00000270722.10	NP_071397.3	Q9HAZ2-1
PRDM16	NM_022114.4 link	c.-14C>T		5_prime_UTR_variant	Exon 1 of 17	ENST00000270722.10	NP_071397.3	Q9HAZ2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10 link	c.-14C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 17	1	NM_022114.4	ENSP00000270722.5		Q9HAZ2-1
PRDM16	ENST00000270722.10 link	c.-14C>T		5_prime_UTR_variant	Exon 1 of 17	1	NM_022114.4	ENSP00000270722.5		Q9HAZ2-1

Frequencies

GnomAD3 genomes

AF:

0.0000999

AC:

AN:

150114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000341

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000659

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD2 exomes

AF:

0.0000377

AC:

AN:

212400

AF XY:

0.0000425

show subpopulations

Gnomad AFR exome

AF:

0.000636

Gnomad AMR exome

AF:

0.0000337

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000112

AC:

AN:

1423086

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

707024

show subpopulations

African (AFR)

AF:

0.000386

AC:

AN:

31054

American (AMR)

AF:

0.0000246

AC:

AN:

40598

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25298

East Asian (EAS)

AF:

0.0000282

AC:

AN:

35434

South Asian (SAS)

AF:

0.00

AC:

AN:

82166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5590

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1094034

Other (OTH)

AF:

0.0000342

AC:

AN:

58530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000999

AC:

AN:

150114

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

73124

show subpopulations

African (AFR)

AF:

0.000341

AC:

AN:

41092

American (AMR)

AF:

0.0000659

AC:

AN:

15176

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3426

East Asian (EAS)

AF:

0.00

AC:

AN:

4998

South Asian (SAS)

AF:

0.00

AC:

AN:

4790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10282

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67064

Other (OTH)

AF:

0.00

AC:

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000136

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

2.5

PromoterAI

-0.030

Neutral

(source)

Mutation Taster

=296/4

polymorphism

(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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1-3069246-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over