rs199853370

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_022114.4(PRDM16):​c.3102C>T​(p.Asn1034Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,613,524 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0021 ( 11 hom. )

Consequence

PRDM16
NM_022114.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -1.06
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 -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
Variant 1-3425743-C-T is Benign according to our data. Variant chr1-3425743-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 241428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-3425743-C-T is described in Lovd as [Benign]. Variant chr1-3425743-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-1.06 with no splicing effect.
BS2
High AC in GnomAd4 at 228 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRDM16NM_022114.4 linkc.3102C>T p.Asn1034Asn synonymous_variant Exon 13 of 17 ENST00000270722.10 NP_071397.3 Q9HAZ2-1
PRDM16NM_199454.3 linkc.3102C>T p.Asn1034Asn synonymous_variant Exon 13 of 17 NP_955533.2 Q9HAZ2-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRDM16ENST00000270722.10 linkc.3102C>T p.Asn1034Asn synonymous_variant Exon 13 of 17 1 NM_022114.4 ENSP00000270722.5 Q9HAZ2-1

Frequencies

GnomAD3 genomes
AF:
0.00151
AC:
229
AN:
152154
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000410
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00151
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00228
Gnomad FIN
AF:
0.00443
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.00184
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.00181
AC:
451
AN:
248886
Hom.:
2
AF XY:
0.00203
AC XY:
274
AN XY:
135158
show subpopulations
Gnomad AFR exome
AF:
0.0000647
Gnomad AMR exome
AF:
0.00125
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00173
Gnomad FIN exome
AF:
0.00627
Gnomad NFE exome
AF:
0.00176
Gnomad OTH exome
AF:
0.00331
GnomAD4 exome
AF:
0.00213
AC:
3117
AN:
1461252
Hom.:
11
Cov.:
32
AF XY:
0.00215
AC XY:
1566
AN XY:
726978
show subpopulations
Gnomad4 AFR exome
AF:
0.000299
Gnomad4 AMR exome
AF:
0.00119
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00168
Gnomad4 FIN exome
AF:
0.00661
Gnomad4 NFE exome
AF:
0.00214
Gnomad4 OTH exome
AF:
0.00268
GnomAD4 genome
AF:
0.00150
AC:
228
AN:
152272
Hom.:
1
Cov.:
32
AF XY:
0.00145
AC XY:
108
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.000409
Gnomad4 AMR
AF:
0.00150
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00228
Gnomad4 FIN
AF:
0.00443
Gnomad4 NFE
AF:
0.00184
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.00151
Hom.:
0
Bravo
AF:
0.00159
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.00245
EpiControl
AF:
0.00284

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:6
Oct 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

PRDM16: BP4, BP7 -

-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Aug 05, 2019
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Nov 21, 2024
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

not specified Benign:2
-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Clinical Genetics, Academic Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Left ventricular noncompaction 8 Benign:2
May 02, 2022
Fulgent Genetics, Fulgent Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jan 31, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

PRDM16-related disorder Benign:1
May 20, 2019
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
CADD
Benign
3.4
DANN
Benign
0.81

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.

Other links and lift over

dbSNP: rs199853370; hg19: chr1-3342307; COSMIC: COSV54587101; API