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rs758774731

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_022114.4(PRDM16):​c.3369_3371dup​(p.Asp1124dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.000299 in 1,613,700 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. E1121E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00035 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00029 ( 3 hom. )

Consequence

PRDM16
NM_022114.4 inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.62
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6
Variant 1-3430950-G-GGAC is Benign according to our data. Variant chr1-3430950-G-GGAC is described in ClinVar as [Likely_benign]. Clinvar id is 413868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 53 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRDM16NM_022114.4 linkuse as main transcriptc.3369_3371dup p.Asp1124dup inframe_insertion 15/17 ENST00000270722.10
PRDM16NM_199454.3 linkuse as main transcriptc.3369_3371dup p.Asp1124dup inframe_insertion 15/17

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRDM16ENST00000270722.10 linkuse as main transcriptc.3369_3371dup p.Asp1124dup inframe_insertion 15/171 NM_022114.4 P1Q9HAZ2-1

Frequencies

GnomAD3 genomes
AF:
0.000348
AC:
53
AN:
152234
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.0121
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000514
AC:
127
AN:
247138
Hom.:
0
AF XY:
0.000469
AC XY:
63
AN XY:
134192
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000204
Gnomad ASJ exome
AF:
0.0106
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000898
Gnomad OTH exome
AF:
0.000663
GnomAD4 exome
AF:
0.000294
AC:
429
AN:
1461348
Hom.:
3
Cov.:
32
AF XY:
0.000316
AC XY:
230
AN XY:
726926
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.0113
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000657
Gnomad4 OTH exome
AF:
0.000828
GnomAD4 genome
AF:
0.000348
AC:
53
AN:
152352
Hom.:
1
Cov.:
33
AF XY:
0.000282
AC XY:
21
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.0000240
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.0121
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.00203
Hom.:
0
Bravo
AF:
0.000344
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000119

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Likely benign, criteria provided, single submitterclinical testingGeneDxNov 16, 2017This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineJun 28, 2017p.Asp1125dup in exon 15 of PRDM16: This variant is not expected to have clinical significance as it is present in 1.077% of Ashkenazi Jewish chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs7 58774731). This variant represents an inframe duplication in a repetitive region containing several aspartic acids (Asp). -
Left ventricular noncompaction 8 Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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.

Other links and lift over

dbSNP: rs758774731; hg19: chr1-3347514; API