rs17390167

chr1-3178267-C-G

Variant summary

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

The NM_022114.4(PRDM16):c.38-7858C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 149,942 control chromosomes in the GnomAD database, including 178 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 0.053 (178 hom., cov: 33)
• Consequence: PRDM16 NM_022114.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM16	NM_022114.4	c.38-7858C>G		intron_variant		ENST00000270722.10
PRDM16	NM_199454.3	c.38-7858C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM16	ENST00000270722.10	c.38-7858C>G		intron_variant		1	NM_022114.4	P1

Frequencies

GnomAD3 genomes AF: 0.0532 AC: 7974 AN: 149820 Hom.: 175 Cov.: 33

Gnomad AFR AF: 0.0447

Gnomad AMI AF: 0.0710

Gnomad AMR AF: 0.0719

Gnomad ASJ AF: 0.0439

Gnomad EAS AF: 0.0437

Gnomad SAS AF: 0.0561

Gnomad FIN AF: 0.0483

Gnomad MID AF: 0.0131

Gnomad NFE AF: 0.0560

Gnomad OTH AF: 0.0502

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

GnomAD4 genome AF: 0.0534 AC: 8000 AN: 149942 Hom.: 178 Cov.: 33 AF XY: 0.0531 AC XY: 3890 AN XY: 73262

Gnomad4 AFR AF: 0.0451

Gnomad4 AMR AF: 0.0719

Gnomad4 ASJ AF: 0.0439

Gnomad4 EAS AF: 0.0434

Gnomad4 SAS AF: 0.0574

Gnomad4 FIN AF: 0.0483

Gnomad4 NFE AF: 0.0560

Gnomad4 OTH AF: 0.0501

Alfa AF: 0.0553 Hom.: 28

Bravo AF: 0.0535

Asia WGS AF: 0.0470 AC: 162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.22
Dann	Benign	0.43

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: rs17390167; hg19: chr1-3094831;