5-123090182-C-G
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_001136239.4(PRDM6):c.168C>G(p.Pro56=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,476,422 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0065 ( 10 hom., cov: 33)
Exomes 𝑓: 0.00056 ( 6 hom. )
Consequence
PRDM6
NM_001136239.4 synonymous
NM_001136239.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.59
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]
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=-0.68).
BP6
?
Variant 5-123090182-C-G is Benign according to our data. Variant chr5-123090182-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2600724.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-2.59 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00645 (976/151302) while in subpopulation AFR AF= 0.0223 (922/41424). AF 95% confidence interval is 0.0211. There are 10 homozygotes in gnomad4. There are 462 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 976 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRDM6 | NM_001136239.4 | c.168C>G | p.Pro56= | synonymous_variant | 2/8 | ENST00000407847.5 | |
PRDM6-AS1 | NR_146771.1 | n.135G>C | non_coding_transcript_exon_variant | 1/2 | |||
PRDM6 | XM_047417878.1 | c.168C>G | p.Pro56= | synonymous_variant | 2/4 | ||
PRDM6 | XR_001742346.2 | n.462C>G | non_coding_transcript_exon_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM6 | ENST00000407847.5 | c.168C>G | p.Pro56= | synonymous_variant | 2/8 | 5 | NM_001136239.4 | P1 | |
PRDM6-AS1 | ENST00000458103.2 | n.118G>C | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00646 AC: 976AN: 151194Hom.: 10 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
976
AN:
151194
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000790 AC: 66AN: 83572Hom.: 0 AF XY: 0.000717 AC XY: 34AN XY: 47428
GnomAD3 exomes
AF:
AC:
66
AN:
83572
Hom.:
AF XY:
AC XY:
34
AN XY:
47428
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000564 AC: 748AN: 1325120Hom.: 6 Cov.: 42 AF XY: 0.000484 AC XY: 316AN XY: 653224
GnomAD4 exome
AF:
AC:
748
AN:
1325120
Hom.:
Cov.:
42
AF XY:
AC XY:
316
AN XY:
653224
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00645 AC: 976AN: 151302Hom.: 10 Cov.: 33 AF XY: 0.00624 AC XY: 462AN XY: 74004
GnomAD4 genome
?
AF:
AC:
976
AN:
151302
Hom.:
Cov.:
33
AF XY:
AC XY:
462
AN XY:
74004
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 08, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at