1-3417934-G-C

Variant names:

• chr1-3417934-G-C
• rs572092688
• NM_022114.4:c.2798G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_022114.4(PRDM16):​c.2798G>C​(p.Arg933Pro) variant causes a missense change involving the alteration of a conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R933W) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRDM16 NM_022114.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.44

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM16	NM_022114.4	c.2798G>C	p.Arg933Pro	missense_variant	Exon 11 of 17	ENST00000270722.10	NP_071397.3
PRDM16	NM_199454.3	c.2798G>C	p.Arg933Pro	missense_variant	Exon 11 of 17		NP_955533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10	c.2798G>C	p.Arg933Pro	missense_variant	Exon 11 of 17	1	NM_022114.4	ENSP00000270722.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 143864 Hom.: 0 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000151 AC: 2 AN: 1324160 Hom.: 0 Cov.: 35 AF XY: 0.00000152 AC XY: 1 AN XY: 659130

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000240

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 143958 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 70036

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T;.;.;D;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.49	T;T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.1	.;M;.;M;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.6	D;D;D;D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Uncertain	0.051	T;D;T;D;T
Polyphen		0.16, 1.0	.;B;.;D;.
Vest4		0.86
MutPred		0.25		.;Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);.;
MVP		0.50
MPC		1.4
ClinPred		1.0	D
GERP RS		4.6
Varity_R		0.76
gMVP		0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs572092688; hg19: chr1-3334498;