GeneBe

5-123090166-AGCCGCC-AGCC

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PM4_Supporting

The NM_001136239.4(PRDM6):​c.165_167delGCC​(p.Pro56del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000976 in 1,485,592 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

PRDM6
NM_001136239.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.42

Publications

2 publications found
Variant links:
Genes affected
PRDM6 (HGNC:9350): (PR/SET domain 6) The protein encoded by this gene is a transcriptional repressor and a member of the PRDM family. Family members contain a PR domain and multiple zinc-finger domains. The encoded protein is involved in regulation of vascular smooth muscle cells (VSMC) contractile proteins. Mutations in this gene result in patent ductus arteriosus 3 (PDA3). [provided by RefSeq, Apr 2017]
PRDM6-AS1 (HGNC:55869): (PRDM6 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM4
Nonframeshift variant in NON repetitive region in NM_001136239.4. Strenght limited to Supporting due to length of the change: 1aa.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136239.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PRDM6
NM_001136239.4
MANE Select
c.165_167delGCCp.Pro56del
disruptive_inframe_deletion
Exon 2 of 8NP_001129711.1Q9NQX0-3
PRDM6-AS1
NR_146771.1
n.148_150delGGC
non_coding_transcript_exon
Exon 1 of 2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PRDM6
ENST00000407847.5
TSL:5 MANE Select
c.165_167delGCCp.Pro56del
disruptive_inframe_deletion
Exon 2 of 8ENSP00000384725.3Q9NQX0-3
PRDM6
ENST00000890813.1
c.165_167delGCCp.Pro56del
disruptive_inframe_deletion
Exon 1 of 7ENSP00000560872.1
PRDM6-AS1
ENST00000458103.3
TSL:2
n.131_133delGGC
non_coding_transcript_exon
Exon 1 of 2

Frequencies

GnomAD3 genomes
AF:
0.00000674
AC:
1
AN:
148450
Hom.:
0
Cov.:
32
show subpopulations
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000597
AC:
52
AN:
87172
AF XY:
0.000505
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000718
Gnomad ASJ exome
AF:
0.000484
Gnomad EAS exome
AF:
0.00210
Gnomad FIN exome
AF:
0.000405
Gnomad NFE exome
AF:
0.000498
Gnomad OTH exome
AF:
0.000838
GnomAD4 exome
AF:
0.000108
AC:
144
AN:
1337028
Hom.:
0
AF XY:
0.000117
AC XY:
77
AN XY:
658892
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.000114
AC:
3
AN:
26300
American (AMR)
AF:
0.000606
AC:
17
AN:
28070
Ashkenazi Jewish (ASJ)
AF:
0.000303
AC:
7
AN:
23086
East Asian (EAS)
AF:
0.000136
AC:
4
AN:
29356
South Asian (SAS)
AF:
0.000357
AC:
26
AN:
72786
European-Finnish (FIN)
AF:
0.000179
AC:
8
AN:
44778
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4556
European-Non Finnish (NFE)
AF:
0.0000712
AC:
75
AN:
1052954
Other (OTH)
AF:
0.0000725
AC:
4
AN:
55142
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.259
Heterozygous variant carriers
0
22
44
65
87
109
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome 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
GnomAD4 genome
AF:
0.00000673
AC:
1
AN:
148564
Hom.:
0
Cov.:
32
AF XY:
0.0000137
AC XY:
1
AN XY:
72736
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
38302
American (AMR)
AF:
0.00
AC:
0
AN:
15150
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5128
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4802
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10546
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
67898
Other (OTH)
AF:
0.00
AC:
0
AN:
2070
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00159
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.4
Mutation Taster
=77/23
polymorphism

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

Other links and lift over

dbSNP: rs563892036; hg19: chr5-122425861; API
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