rs372189819

Variant names:

• chr1-3412645-C-T
• rs372189819
• NM_022114.4:c.2448C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-3412645-C-T
• chr1-3412645-C-G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_022114.4(PRDM16):​c.2448C>T​(p.Asn816Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,548,904 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (18 hom.)
• Consequence: PRDM16 NM_022114.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -1.43
• Publications: 2 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):

• dilated cardiomyopathy

  Inheritance: AD Classification: STRONG Submitted by: ClinGen
• left ventricular noncompaction 8

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

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 1-3412645-C-T is Benign according to our data. Variant chr1-3412645-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 388234.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.42 with no splicing effect.
• BS2: High AC in GnomAd4 at 311 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022114.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM16	NM_022114.4	MANE Select	c.2448C>T	p.Asn816Asn	synonymous	Exon 9 of 17	NP_071397.3
	PRDM16	NM_199454.3		c.2448C>T	p.Asn816Asn	synonymous	Exon 9 of 17	NP_955533.2	Q9HAZ2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM16	ENST00000270722.10	TSL:1 MANE Select	c.2448C>T	p.Asn816Asn	synonymous	Exon 9 of 17	ENSP00000270722.5	Q9HAZ2-1
	PRDM16	ENST00000378391.6	TSL:1	c.2448C>T	p.Asn816Asn	synonymous	Exon 9 of 17	ENSP00000367643.2	Q9HAZ2-2
	PRDM16	ENST00000512462.5	TSL:1	n.2226C>T		non_coding_transcript_exon	Exon 8 of 16

Frequencies

GnomAD3 genomes AF: 0.00204 AC: 311 AN: 152252 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000940

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00292

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00316

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00270 AC: 448 AN: 165908 AF XY: 0.00282

Gnomad AFR exome AF: 0.000936

Gnomad AMR exome AF: 0.000950

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000799

Gnomad FIN exome AF: 0.00452

Gnomad NFE exome AF: 0.00434

Gnomad OTH exome AF: 0.00311

GnomAD4 exome AF: 0.00424 AC: 5919 AN: 1396534 Hom.: 18 Cov.: 36 AF XY: 0.00413 AC XY: 2843 AN XY: 689070

African (AFR) AF: 0.000546 AC: 17 AN: 31142

American (AMR) AF: 0.000698 AC: 25 AN: 35824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23958

East Asian (EAS) AF: 0.000108 AC: 4 AN: 36990

South Asian (SAS) AF: 0.000940 AC: 75 AN: 79808

European-Finnish (FIN) AF: 0.00370 AC: 171 AN: 46186

Middle Eastern (MID) AF: 0.00359 AC: 20 AN: 5564

European-Non Finnish (NFE) AF: 0.00505 AC: 5456 AN: 1079674

Other (OTH) AF: 0.00263 AC: 151 AN: 57388

GnomAD4 genome AF: 0.00204 AC: 311 AN: 152370 Hom.: 0 Cov.: 33 AF XY: 0.00200 AC XY: 149 AN XY: 74500

African (AFR) AF: 0.000938 AC: 39 AN: 41594

American (AMR) AF: 0.000588 AC: 9 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4834

European-Finnish (FIN) AF: 0.00292 AC: 31 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00316 AC: 215 AN: 68034

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00116 Hom.: 0

Bravo AF: 0.00214

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not provided (6)
-	-	5	not specified (5)
-	-	1	Left ventricular noncompaction 8 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	4.7
DANN	Benign	0.95
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

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: rs372189819; hg19: chr1-3329209; COSMIC: COSV54592610;