rs10492939

Positions:

• chr1-3386307-G-A

Variant summary

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

The ENST00000270722.10(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 ENST00000270722.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM16	NM_022114.4	c.573+1021G>A		intron_variant		ENST00000270722.10	NP_071397.3
PRDM16	NM_199454.3	c.573+1021G>A		intron_variant			NP_955533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10	c.573+1021G>A		intron_variant		1	NM_022114.4	ENSP00000270722	P1

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

Gnomad4 AFR AF: 0.0804

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.251

Alfa AF: 0.279 Hom.: 3638

Bravo AF: 0.238

Asia WGS AF: 0.526 AC: 1827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.015
DANN	Benign	0.71

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: rs10492939; hg19: chr1-3302871;