Variant 1-3417951-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_022114.4(PRDM16):c.2815C>T(p.Leu939Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,460,856 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L939I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PRDM16
NM_022114.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.60

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM16	NM_022114.4 linkuse as main transcript	c.2815C>T	p.Leu939Phe	missense_variant	11/17	ENST00000270722.10
PRDM16	NM_199454.3 linkuse as main transcript	c.2815C>T	p.Leu939Phe	missense_variant	11/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM16	ENST00000270722.10 linkuse as main transcript	c.2815C>T	p.Leu939Phe	missense_variant	11/17	1	NM_022114.4	P1	Q9HAZ2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

246430

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134164

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460856

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726712

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

T;.;.;T;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.88

D;D;D;D;D

M_CAP

Benign

0.055

MetaRNN

Uncertain

0.46

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

.;M;.;M;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-2.3

N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.032

D;D;D;D;D

Sift4G

Benign

0.11

T;T;T;T;T

Polyphen

0.89, 1.0

.;P;.;D;.

Vest4

0.82

MutPred

0.23

.;Loss of catalytic residue at L939 (P = 0.0102);Loss of catalytic residue at L939 (P = 0.0102);Loss of catalytic residue at L939 (P = 0.0102);.;

MVP

0.65

MPC

1.0

ClinPred

0.96

GERP RS

4.7

Varity_R

0.21

gMVP

0.57

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over