1-3167148-T-C

Variant summary

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

The NM_022114.4(PRDM16):c.38-18977T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,860 control chromosomes in the GnomAD database, including 20,851 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 0.51 (20851 hom., cov: 33)
• Consequence: PRDM16 NM_022114.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM16	NM_022114.4	c.38-18977T>C		intron_variant		ENST00000270722.10
PRDM16	NM_199454.3	c.38-18977T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM16	ENST00000270722.10	c.38-18977T>C		intron_variant		1	NM_022114.4	P1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77436 AN: 151744 Hom.: 20835 Cov.: 33

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.510 AC: 77491 AN: 151860 Hom.: 20851 Cov.: 33 AF XY: 0.510 AC XY: 37818 AN XY: 74202

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.512

Alfa AF: 0.445 Hom.: 26129

Bravo AF: 0.526

Asia WGS AF: 0.433 AC: 1502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.014
Dann	Benign	0.31

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: rs2651899; hg19: chr1-3083712;