1-3426240-G-T

Variant names:

• chr1-3426240-G-T
• rs870171
• NM_022114.4:c.3284+15G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022114.4(PRDM16):​c.3284+15G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,607,588 control chromosomes in the GnomAD database, including 70,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8231 hom., cov: 31)
  • Exomes 𝑓: 0.29 (61834 hom.)
• Consequence: PRDM16 NM_022114.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.15
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-3426240-G-T is Benign according to our data. Variant chr1-3426240-G-T is described in ClinVar as Benign. ClinVar VariationId is 227035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 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.3284+15G>T		intron	N/A	NP_071397.3
	PRDM16	NM_199454.3		c.3284+15G>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.3284+15G>T		intron	N/A	ENSP00000270722.5	Q9HAZ2-1
	PRDM16	ENST00000378391.6	TSL:1	c.3284+15G>T		intron	N/A	ENSP00000367643.2	Q9HAZ2-2
	PRDM16	ENST00000512462.5	TSL:1	n.3062+15G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48586 AN: 151736 Hom.: 8215 Cov.: 31

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.325

GnomAD2 exomes AF: 0.295 AC: 72759 AN: 246792 AF XY: 0.291

Gnomad AFR exome AF: 0.419

Gnomad AMR exome AF: 0.280

Gnomad ASJ exome AF: 0.274

Gnomad EAS exome AF: 0.499

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.269

Gnomad OTH exome AF: 0.289

GnomAD4 exome AF: 0.288 AC: 419424 AN: 1455734 Hom.: 61834 Cov.: 31 AF XY: 0.287 AC XY: 207530 AN XY: 723644

African (AFR) AF: 0.419 AC: 13967 AN: 33310

American (AMR) AF: 0.285 AC: 12679 AN: 44490

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 7112 AN: 25930

East Asian (EAS) AF: 0.433 AC: 17140 AN: 39602

South Asian (SAS) AF: 0.277 AC: 23774 AN: 85912

European-Finnish (FIN) AF: 0.227 AC: 12090 AN: 53162

Middle Eastern (MID) AF: 0.264 AC: 1518 AN: 5746

European-Non Finnish (NFE) AF: 0.283 AC: 312882 AN: 1107454

Other (OTH) AF: 0.304 AC: 18262 AN: 60128

GnomAD4 genome AF: 0.320 AC: 48655 AN: 151854 Hom.: 8231 Cov.: 31 AF XY: 0.317 AC XY: 23505 AN XY: 74194

African (AFR) AF: 0.420 AC: 17394 AN: 41420

American (AMR) AF: 0.300 AC: 4586 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 898 AN: 3464

East Asian (EAS) AF: 0.483 AC: 2469 AN: 5114

South Asian (SAS) AF: 0.277 AC: 1330 AN: 4810

European-Finnish (FIN) AF: 0.230 AC: 2428 AN: 10548

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18611 AN: 67914

Other (OTH) AF: 0.326 AC: 686 AN: 2102

Alfa AF: 0.282 Hom.: 13895

Bravo AF: 0.331

Asia WGS AF: 0.395 AC: 1371 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	2	Left ventricular noncompaction 8 (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.20
PhyloP100		-1.1
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: rs870171; hg19: chr1-3342804; COSMIC: COSV107215302; COSMIC: COSV107215302;