1-3189833-C-T

Variant names:

• chr1-3189833-C-T
• rs2651916
• NM_022114.4:c.387+3359C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022114.4(PRDM16):​c.387+3359C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 152,162 control chromosomes in the GnomAD database, including 60,342 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 0.89 (60342 hom., cov: 32)
• Consequence: PRDM16 NM_022114.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 1 publications found

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):

• dilated cardiomyopathy

  Inheritance: AD Classification: STRONG Submitted by: ClinGen
• left ventricular noncompaction 8

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• left ventricular noncompaction

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC107984909 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022114.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM16	NM_022114.4	MANE Select	c.387+3359C>T		intron	N/A	NP_071397.3
	PRDM16	NM_199454.3		c.387+3359C>T		intron	N/A	NP_955533.2	Q9HAZ2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM16	ENST00000270722.10	TSL:1 MANE Select	c.387+3359C>T		intron	N/A	ENSP00000270722.5	Q9HAZ2-1
	PRDM16	ENST00000378391.6	TSL:1	c.387+3359C>T		intron	N/A	ENSP00000367643.2	Q9HAZ2-2
	PRDM16	ENST00000511072.5	TSL:5	c.387+3359C>T		intron	N/A	ENSP00000426975.1	D6RDW0

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135271 AN: 152046 Hom.: 60324 Cov.: 32

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.905

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.952

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.897

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

GnomAD4 genome AF: 0.889 AC: 135341 AN: 152162 Hom.: 60342 Cov.: 32 AF XY: 0.889 AC XY: 66115 AN XY: 74364

African (AFR) AF: 0.820 AC: 34045 AN: 41504

American (AMR) AF: 0.904 AC: 13821 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3044 AN: 3470

East Asian (EAS) AF: 0.899 AC: 4629 AN: 5150

South Asian (SAS) AF: 0.845 AC: 4066 AN: 4814

European-Finnish (FIN) AF: 0.952 AC: 10079 AN: 10590

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.921 AC: 62666 AN: 68020

Other (OTH) AF: 0.898 AC: 1898 AN: 2114

Alfa AF: 0.908 Hom.: 12737

Bravo AF: 0.883

Asia WGS AF: 0.860 AC: 2990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.014
DANN	Benign	0.44
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2651916; hg19: chr1-3106397; COSMIC: COSV54584276; COSMIC: COSV54584276;