rs200234106

chr1-3425593-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_022114.4(PRDM16):c.2952C>T(p.Cys984=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000283 in 1,613,628 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (2 hom.)
• Consequence: PRDM16 NM_022114.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.990

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 1-3425593-C-T is Benign according to our data. Variant chr1-3425593-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 474424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.99 with no splicing effect.
• BS2: High AC in GnomAd at 50 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM16	NM_022114.4	c.2952C>T	p.Cys984=	synonymous_variant	13/17	ENST00000270722.10
PRDM16	NM_199454.3	c.2952C>T	p.Cys984=	synonymous_variant	13/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM16	ENST00000270722.10	c.2952C>T	p.Cys984=	synonymous_variant	13/17	1	NM_022114.4	P1

Frequencies

GnomAD3 genomes AF: 0.000329 AC: 50 AN: 152126 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000485 AC: 121 AN: 249270 Hom.: 0 AF XY: 0.000554 AC XY: 75 AN XY: 135292

Gnomad AFR exome AF: 0.000194

Gnomad AMR exome AF: 0.000725

Gnomad ASJ exome AF: 0.00348

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.00105

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000203

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000278 AC: 406 AN: 1461502 Hom.: 2 Cov.: 32 AF XY: 0.000290 AC XY: 211 AN XY: 727102

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000805

Gnomad4 ASJ exome AF: 0.00287

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00123

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000109

Gnomad4 OTH exome AF: 0.000679

GnomAD4 genome AF: 0.000329 AC: 50 AN: 152126 Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25 AN XY: 74324

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.000957

Alfa AF: 0.000630 Hom.: 0

Bravo AF: 0.000434

EpiCase AF: 0.000545

EpiControl AF: 0.000356

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 25, 2020

- -

Left ventricular noncompaction 8 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
Cadd	Benign	14
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs200234106; hg19: chr1-3342157; COSMIC: COSV54599152;