NM_022114.4:c.573+1021G>A

Variant names:

• chr1-3386307-G-A
• rs10492939
• NM_022114.4:c.573+1021G>A

Variant summary

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

The NM_022114.4(PRDM16):​c.573+1021G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,170 control chromosomes in the GnomAD database, including 5,919 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 0.25 (5919 hom., cov: 33)
• Consequence: PRDM16 NM_022114.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM16	NM_022114.4	MANE Select	c.573+1021G>A		intron	N/A	NP_071397.3
	PRDM16	NM_199454.3		c.573+1021G>A		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.573+1021G>A		intron	N/A	ENSP00000270722.5
	PRDM16	ENST00000378391.6	TSL:1	c.573+1021G>A		intron	N/A	ENSP00000367643.2
	PRDM16	ENST00000512462.5	TSL:1	n.351+1021G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37604 AN: 152052 Hom.: 5929 Cov.: 33

Gnomad AFR AF: 0.0805

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.247 AC: 37605 AN: 152170 Hom.: 5919 Cov.: 33 AF XY: 0.258 AC XY: 19227 AN XY: 74382

African (AFR) AF: 0.0804 AC: 3341 AN: 41540

American (AMR) AF: 0.337 AC: 5155 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 740 AN: 3468

East Asian (EAS) AF: 0.606 AC: 3133 AN: 5170

South Asian (SAS) AF: 0.518 AC: 2502 AN: 4826

European-Finnish (FIN) AF: 0.308 AC: 3246 AN: 10554

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

European-Non Finnish (NFE) AF: 0.274 AC: 18597 AN: 67994

Other (OTH) AF: 0.251 AC: 530 AN: 2114

Alfa AF: 0.280 Hom.: 5159

Bravo AF: 0.238

Asia WGS AF: 0.526 AC: 1827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.015
DANN	Benign	0.71
PhyloP100		-1.0
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: rs10492939; hg19: chr1-3302871;