1-3271579-C-G

Variant names:

• chr1-3271579-C-G
• rs2455122
• NM_022114.4:c.438+27442C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022114.4(PRDM16):​c.438+27442C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,118 control chromosomes in the GnomAD database, including 10,221 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 0.29 (10221 hom., cov: 33)
• Consequence: PRDM16 NM_022114.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• Publications: 3 publications found

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]

PRDM16 Gene-Disease associations (from GenCC):

• left ventricular noncompaction 8

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• left ventricular noncompaction

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

LOC124903828 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM16	NM_022114.4	c.438+27442C>G		intron_variant	Intron 3 of 16	ENST00000270722.10	NP_071397.3
LOC124903828	XM_047436627.1	c.-15240C>G		5_prime_UTR_variant	Exon 1 of 2		XP_047292583.1
PRDM16	NM_199454.3	c.438+27442C>G		intron_variant	Intron 3 of 16		NP_955533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10	c.438+27442C>G		intron_variant	Intron 3 of 16	1	NM_022114.4	ENSP00000270722.5

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43903 AN: 152000 Hom.: 10189 Cov.: 33

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.289 AC: 44000 AN: 152118 Hom.: 10221 Cov.: 33 AF XY: 0.286 AC XY: 21289 AN XY: 74374

African (AFR) AF: 0.633 AC: 26213 AN: 41442

American (AMR) AF: 0.327 AC: 5005 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 723 AN: 3470

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5184

South Asian (SAS) AF: 0.147 AC: 707 AN: 4824

European-Finnish (FIN) AF: 0.111 AC: 1175 AN: 10596

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9457 AN: 67994

Other (OTH) AF: 0.265 AC: 560 AN: 2110

Alfa AF: 0.208 Hom.: 700

Bravo AF: 0.319

Asia WGS AF: 0.119 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.40
PhyloP100		-0.093
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2455122; hg19: chr1-3188143;