1-3068981-G-T

Variant names:

• chr1-3068981-G-T
• rs868744430
• ENST00000687743.2:n.117C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000687743.2(PRDM16-DT):​n.117C>A variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.000288 in 145,584 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00029 (0 hom., cov: 25)
• Consequence: PRDM16-DT ENST00000687743.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.93
• Publications: 0 publications found

Genes affected

PRDM16-DT (HGNC:48664): (PRDM16 divergent transcript)

LOC124903827 (HGNC:):

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM16	NM_022114.4	c.-279G>T		upstream_gene_variant		ENST00000270722.10	NP_071397.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10	c.-279G>T		upstream_gene_variant		1	NM_022114.4	ENSP00000270722.5

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 42 AN: 145476 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000677

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00144

Gnomad SAS AF: 0.000221

Gnomad FIN AF: 0.0000992

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000316

Gnomad OTH AF: 0.000503

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

GnomAD4 genome AF: 0.000288 AC: 42 AN: 145584 Hom.: 0 Cov.: 25 AF XY: 0.000310 AC XY: 22 AN XY: 70954

African (AFR) AF: 0.0000262 AC: 1 AN: 38204

American (AMR) AF: 0.000676 AC: 10 AN: 14790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00144 AC: 7 AN: 4854

South Asian (SAS) AF: 0.000221 AC: 1 AN: 4530

European-Finnish (FIN) AF: 0.0000992 AC: 1 AN: 10076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000316 AC: 21 AN: 66504

Other (OTH) AF: 0.000497 AC: 1 AN: 2012

Alfa AF: 0.00 Hom.: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	17
DANN	Benign	0.84
PhyloP100		3.9
PromoterAI		-0.051	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs868744430; hg19: chr1-2985545;