Genetic Variant NM_022114.4:c.438+48795T>C (chr1-3292932-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.438+48795T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,188 control chromosomes in the GnomAD database, including 48,869 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 0.80 ( 48869 hom., cov: 33)

Consequence

PRDM16
NM_022114.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.849

Publications

5 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:

LOC124903828 (HGNC:):

LOC124903828 links:

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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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PRDM16	NM_022114.4 link	c.438+48795T>C	intron_variant	Intron 3 of 16	ENST00000270722.10	NP_071397.3	Q9HAZ2-1
LOC124903828	XM_047436627.1 link	c.*4950T>C	3_prime_UTR_variant	Exon 1 of 2		XP_047292583.1
PRDM16	NM_199454.3 link	c.438+48795T>C	intron_variant	Intron 3 of 16		NP_955533.2	Q9HAZ2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10 link	c.438+48795T>C		intron_variant	Intron 3 of 16	1	NM_022114.4	ENSP00000270722.5		Q9HAZ2-1

Frequencies

GnomAD3 genomes

AF:

0.799

AC:

121562

AN:

152070

Hom.:

48804

Cov.:

show subpopulations

Gnomad AFR

AF:

0.822

Gnomad AMI

AF:

0.791

Gnomad AMR

AF:

0.829

Gnomad ASJ

AF:

0.713

Gnomad EAS

AF:

0.994

Gnomad SAS

AF:

0.715

Gnomad FIN

AF:

0.816

Gnomad MID

AF:

0.722

Gnomad NFE

AF:

0.773

Gnomad OTH

AF:

0.785

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

GnomAD4 genome

AF:

0.800

AC:

121690

AN:

152188

Hom.:

48869

Cov.:

AF XY:

0.800

AC XY:

59563

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.822

AC:

34155

AN:

41534

American (AMR)

AF:

0.829

AC:

12679

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.713

AC:

2475

AN:

3470

East Asian (EAS)

AF:

0.994

AC:

5125

AN:

5156

South Asian (SAS)

AF:

0.716

AC:

3448

AN:

4818

European-Finnish (FIN)

AF:

0.816

AC:

8646

AN:

10600

Middle Eastern (MID)

AF:

0.724

AC:

213

AN:

294

European-Non Finnish (NFE)

AF:

0.773

AC:

52565

AN:

67998

Other (OTH)

AF:

0.788

AC:

1663

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1280

2559

3839

5118

6398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

874

1748

2622

3496

4370

<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:

0.736

Hom.:

2685

Bravo

AF:

0.805

Asia WGS

AF:

0.876

AC:

3044

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

8.6

(source)

DANN

Benign

0.46

PhyloP100

0.85

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