1-3069544-T-TC

Position:

• chr1-3069544-T-TC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_022114.4(PRDM16):​c.37+256dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00839 in 135,782 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0084 (12 hom., cov: 30)
• Consequence: PRDM16 NM_022114.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 Benign. Variant got -10 ACMG points.

• BP6: Variant 1-3069544-T-TC is Benign according to our data. Variant chr1-3069544-T-TC is described in ClinVar as [Likely_benign]. Clinvar id is 1193752.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00839 (1139/135782) while in subpopulation EAS AF= 0.0358 (141/3934). AF 95% confidence interval is 0.031. There are 12 homozygotes in gnomad4. There are 553 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1139 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM16	NM_022114.4	c.37+256dup		intron_variant		ENST00000270722.10	NP_071397.3
LOC124903827	XM_047436614.1	c.1651-574_1651-573insG		intron_variant			XP_047292570.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10	c.37+256dup		intron_variant		1	NM_022114.4	ENSP00000270722	P1

Frequencies

GnomAD3 genomes AF: 0.00839 AC: 1139 AN: 135706 Hom.: 12 Cov.: 30

Gnomad AFR AF: 0.00270

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.000923

Gnomad EAS AF: 0.0360

Gnomad SAS AF: 0.0152

Gnomad FIN AF: 0.00717

Gnomad MID AF: 0.00350

Gnomad NFE AF: 0.00908

Gnomad OTH AF: 0.00583

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

GnomAD4 genome AF: 0.00839 AC: 1139 AN: 135782 Hom.: 12 Cov.: 30 AF XY: 0.00840 AC XY: 553 AN XY: 65838

Gnomad4 AFR AF: 0.00269

Gnomad4 AMR AF: 0.0141

Gnomad4 ASJ AF: 0.000923

Gnomad4 EAS AF: 0.0358

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.00717

Gnomad4 NFE AF: 0.00908

Gnomad4 OTH AF: 0.00631

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 03, 2020

- -

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;