1-3068981-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000687743.2(PRDM16-DT):​n.117C>G variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.00552 in 145,586 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0055 (11 hom., cov: 25)
• Consequence: PRDM16-DT ENST00000687743.2 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-3068981-G-C is Benign according to our data. Variant chr1-3068981-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1223395.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM16	NM_022114.4	c.-279G>C		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>C		upstream_gene_variant		1	NM_022114.4	ENSP00000270722.5

Frequencies

GnomAD3 genomes AF: 0.00551 AC: 801 AN: 145478 Hom.: 11 Cov.: 25

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00277

Gnomad ASJ AF: 0.00116

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0110

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00173

Gnomad OTH AF: 0.00603

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

GnomAD4 genome AF: 0.00552 AC: 803 AN: 145586 Hom.: 11 Cov.: 25 AF XY: 0.00571 AC XY: 405 AN XY: 70954

African (AFR) AF: 0.0136 AC: 520 AN: 38204

American (AMR) AF: 0.00277 AC: 41 AN: 14792

Ashkenazi Jewish (ASJ) AF: 0.00116 AC: 4 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 4854

South Asian (SAS) AF: 0.00 AC: 0 AN: 4530

European-Finnish (FIN) AF: 0.0110 AC: 111 AN: 10076

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

European-Non Finnish (NFE) AF: 0.00173 AC: 115 AN: 66504

Other (OTH) AF: 0.00596 AC: 12 AN: 2012

Alfa AF: 0.00290 Hom.: 6

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 23, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	17
DANN	Benign	0.68
PhyloP100		3.9
PromoterAI		0.047	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;