chr1-3430950-G-GGAC

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_022114.4(PRDM16):​c.3369_3371dupCGA​(p.Asp1124dup) variant causes a disruptive 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 (★★).

Frequency

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

Consequence

PRDM16
NM_022114.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.62

Publications

0 publications found
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 Gene-Disease associations (from GenCC):
  • left ventricular noncompaction 8
    Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)
  • familial isolated dilated cardiomyopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • left ventricular noncompaction
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • dilated cardiomyopathy
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank MANE Protein UniProt
PRDM16NM_022114.4 linkc.3369_3371dupCGA p.Asp1124dup disruptive_inframe_insertion Exon 15 of 17 ENST00000270722.10 NP_071397.3 Q9HAZ2-1
PRDM16NM_199454.3 linkc.3369_3371dupCGA p.Asp1124dup disruptive_inframe_insertion Exon 15 of 17 NP_955533.2 Q9HAZ2-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRDM16ENST00000270722.10 linkc.3369_3371dupCGA p.Asp1124dup disruptive_inframe_insertion Exon 15 of 17 1 NM_022114.4 ENSP00000270722.5 Q9HAZ2-1

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
GnomAD2 exomes
AF:
0.000514
AC:
127
AN:
247138
AF XY:
0.000469
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 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
African (AFR)
AF:
0.00
AC:
0
AN:
33468
American (AMR)
AF:
0.000224
AC:
10
AN:
44658
Ashkenazi Jewish (ASJ)
AF:
0.0113
AC:
296
AN:
26124
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86164
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53366
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000657
AC:
73
AN:
1111724
Other (OTH)
AF:
0.000828
AC:
50
AN:
60380
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.478
Heterozygous variant carriers
0
25
50
76
101
126
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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
African (AFR)
AF:
0.0000240
AC:
1
AN:
41584
American (AMR)
AF:
0.0000653
AC:
1
AN:
15304
Ashkenazi Jewish (ASJ)
AF:
0.0121
AC:
42
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5186
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.000103
AC:
7
AN:
68034
Other (OTH)
AF:
0.000946
AC:
2
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.486
Heterozygous variant carriers
0
3
6
8
11
14
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Nov 16, 2017
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This 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. -

Jun 28, 2017
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

p.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). -

Feb 16, 2025
Laboratory of Genetics, Children's Clinical University Hospital Latvia
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Left ventricular noncompaction 8 Benign:1
Aug 20, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
4.6
Mutation Taster
=81/19
polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs758774731; hg19: chr1-3347514; API