chr5-123090213-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001136239.4(PRDM6):c.199G>A(p.Asp67Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00105 in 1,479,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00073 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 0 hom. )
Consequence
PRDM6
NM_001136239.4 missense
NM_001136239.4 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: 4.50
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 -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.011134952).
BS2
?
High AC in GnomAd at 111 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRDM6 | NM_001136239.4 | c.199G>A | p.Asp67Asn | missense_variant | 2/8 | ENST00000407847.5 | |
PRDM6-AS1 | NR_146771.1 | n.104C>T | non_coding_transcript_exon_variant | 1/2 | |||
PRDM6 | XM_047417878.1 | c.199G>A | p.Asp67Asn | missense_variant | 2/4 | ||
PRDM6 | XR_001742346.2 | n.493G>A | non_coding_transcript_exon_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM6 | ENST00000407847.5 | c.199G>A | p.Asp67Asn | missense_variant | 2/8 | 5 | NM_001136239.4 | P1 | |
PRDM6-AS1 | ENST00000458103.2 | n.87C>T | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000732 AC: 111AN: 151696Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
111
AN:
151696
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: 0.000612 AC: 51AN: 83364Hom.: 0 AF XY: 0.000527 AC XY: 25AN XY: 47470
GnomAD3 exomes
AF:
AC:
51
AN:
83364
Hom.:
AF XY:
AC XY:
25
AN XY:
47470
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: 0.00108 AC: 1440AN: 1327842Hom.: 0 Cov.: 44 AF XY: 0.00106 AC XY: 697AN XY: 654640
GnomAD4 exome
AF:
AC:
1440
AN:
1327842
Hom.:
Cov.:
44
AF XY:
AC XY:
697
AN XY:
654640
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: 0.000731 AC: 111AN: 151800Hom.: 0 Cov.: 33 AF XY: 0.000647 AC XY: 48AN XY: 74206
GnomAD4 genome
?
AF:
AC:
111
AN:
151800
Hom.:
Cov.:
33
AF XY:
AC XY:
48
AN XY:
74206
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:
ExAC
?
AF:
AC:
3
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 14, 2021 | The c.199G>A (p.D67N) alteration is located in exon 2 (coding exon 1) of the PRDM6 gene. This alteration results from a G to A substitution at nucleotide position 199, causing the aspartic acid (D) at amino acid position 67 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
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