rs541892148

Variant names:

• chr1-3069544-TC-T
• rs541892148
• NM_022114.4:c.37+256delC

Your query was ambiguous. Multiple possible variants found:

• chr1-3069544-TC-T
• chr1-3069544-TC-TCC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_022114.4(PRDM16):​c.37+256delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 135,792 control chromosomes in the GnomAD database, including 6 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0018 (6 hom., cov: 30)
• Consequence: PRDM16 NM_022114.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

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]

LOC124903827 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 248 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM16	NM_022114.4	c.37+256delC		intron_variant	Intron 1 of 16	ENST00000270722.10	NP_071397.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10	c.37+249delC		intron_variant	Intron 1 of 16	1	NM_022114.4	ENSP00000270722.5

Frequencies

GnomAD3 genomes AF: 0.00183 AC: 248 AN: 135716 Hom.: 6 Cov.: 30

Gnomad AFR AF: 0.000572

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000127

Gnomad OTH AF: 0.000530

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

GnomAD4 genome AF: 0.00183 AC: 248 AN: 135792 Hom.: 6 Cov.: 30 AF XY: 0.00263 AC XY: 173 AN XY: 65844

Gnomad4 AFR AF: 0.000571

Gnomad4 AMR AF: 0.0155

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000127

Gnomad4 OTH AF: 0.000526

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs541892148; hg19: chr1-2986108;