1-3377858-A-G

Variant names:

• chr1-3377858-A-G
• rs2493310
• NM_022114.4:c.439-7294A>G

Variant summary

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

The ENST00000270722.10(PRDM16):​c.439-7294A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,114 control chromosomes in the GnomAD database, including 7,872 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 0.27 (7872 hom., cov: 33)
• Consequence: PRDM16 ENST00000270722.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 7 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):

• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000270722.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM16	NM_022114.4	MANE Select	c.439-7294A>G		intron	N/A	NP_071397.3
	PRDM16	NM_199454.3		c.439-7294A>G		intron	N/A	NP_955533.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM16	ENST00000270722.10	TSL:1 MANE Select	c.439-7294A>G		intron	N/A	ENSP00000270722.5
	PRDM16	ENST00000378391.6	TSL:1	c.439-7294A>G		intron	N/A	ENSP00000367643.2
	PRDM16	ENST00000512462.5	TSL:1	n.217-7294A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40649 AN: 151996 Hom.: 7845 Cov.: 33

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0237

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.268 AC: 40726 AN: 152114 Hom.: 7872 Cov.: 33 AF XY: 0.260 AC XY: 19333 AN XY: 74392

African (AFR) AF: 0.551 AC: 22844 AN: 41450

American (AMR) AF: 0.164 AC: 2512 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 651 AN: 3466

East Asian (EAS) AF: 0.0238 AC: 123 AN: 5174

South Asian (SAS) AF: 0.139 AC: 671 AN: 4818

European-Finnish (FIN) AF: 0.134 AC: 1418 AN: 10608

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11806 AN: 67982

Other (OTH) AF: 0.246 AC: 519 AN: 2110

Alfa AF: 0.198 Hom.: 8175

Bravo AF: 0.284

Asia WGS AF: 0.116 AC: 403 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.11
DANN	Benign	0.32
PhyloP100		-1.7
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: rs2493310; hg19: chr1-3294422;