chr1-3363689-G-A

Position:

• chr1-3363689-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022114.4(PRDM16):​c.439-21463G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,074 control chromosomes in the GnomAD database, including 1,516 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 0.12 (1516 hom., cov: 32)
• Consequence: PRDM16 NM_022114.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM16	NM_022114.4	c.439-21463G>A		intron_variant		ENST00000270722.10	NP_071397.3
PRDM16	NM_199454.3	c.439-21463G>A		intron_variant			NP_955533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10	c.439-21463G>A		intron_variant		1	NM_022114.4	ENSP00000270722	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17727 AN: 151956 Hom.: 1510 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0621

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.0315

Gnomad SAS AF: 0.0952

Gnomad FIN AF: 0.0849

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0671

Gnomad OTH AF: 0.0920

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

GnomAD4 genome AF: 0.117 AC: 17762 AN: 152074 Hom.: 1516 Cov.: 32 AF XY: 0.114 AC XY: 8501 AN XY: 74340

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.0618

Gnomad4 ASJ AF: 0.0576

Gnomad4 EAS AF: 0.0318

Gnomad4 SAS AF: 0.0946

Gnomad4 FIN AF: 0.0849

Gnomad4 NFE AF: 0.0671

Gnomad4 OTH AF: 0.0948

Alfa AF: 0.0682 Hom.: 534

Bravo AF: 0.121

Asia WGS AF: 0.0980 AC: 342 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.64
DANN	Benign	0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs6658356; hg19: chr1-3280253;