rs61759167

Variant names:

• chr1-3175023-C-T
• rs61759167
• NM_022114.4:c.38-11102C>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.38-11102C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,142 control chromosomes in the GnomAD database, including 4,128 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 0.23 (4128 hom., cov: 33)
• Consequence: PRDM16 NM_022114.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.755
• Publications: 12 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.284 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.38-11102C>T		intron	N/A	NP_071397.3
	PRDM16	NM_199454.3		c.38-11102C>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.38-11102C>T		intron	N/A	ENSP00000270722.5	Q9HAZ2-1
	PRDM16	ENST00000378391.6	TSL:1	c.38-11102C>T		intron	N/A	ENSP00000367643.2	Q9HAZ2-2
	PRDM16	ENST00000511072.5	TSL:5	c.38-11102C>T		intron	N/A	ENSP00000426975.1	D6RDW0

Frequencies

GnomAD3 genomes AF: 0.230 AC: 35002 AN: 152024 Hom.: 4126 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.230 AC: 35002 AN: 152142 Hom.: 4128 Cov.: 33 AF XY: 0.234 AC XY: 17395 AN XY: 74380

African (AFR) AF: 0.203 AC: 8423 AN: 41502

American (AMR) AF: 0.291 AC: 4453 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 827 AN: 3472

East Asian (EAS) AF: 0.134 AC: 693 AN: 5158

South Asian (SAS) AF: 0.257 AC: 1237 AN: 4812

European-Finnish (FIN) AF: 0.248 AC: 2626 AN: 10594

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15993 AN: 67998

Other (OTH) AF: 0.246 AC: 518 AN: 2108

Alfa AF: 0.227 Hom.: 5188

Bravo AF: 0.229

Asia WGS AF: 0.206 AC: 715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.83
PhyloP100		-0.76
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: rs61759167; hg19: chr1-3091587; COSMIC: COSV54584020;