chr5-123090253-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001136239.4(PRDM6):c.239C>T(p.Ser80Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000484 in 1,486,846 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000048 ( 1 hom. )
Consequence
PRDM6
NM_001136239.4 missense
NM_001136239.4 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: 3.45
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.14868113).
BS2
High AC in GnomAd4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRDM6 | NM_001136239.4 | c.239C>T | p.Ser80Leu | missense_variant | 2/8 | ENST00000407847.5 | |
PRDM6-AS1 | NR_146771.1 | n.64G>A | non_coding_transcript_exon_variant | 1/2 | |||
PRDM6 | XM_047417878.1 | c.239C>T | p.Ser80Leu | missense_variant | 2/4 | ||
PRDM6 | XR_001742346.2 | n.533C>T | non_coding_transcript_exon_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM6 | ENST00000407847.5 | c.239C>T | p.Ser80Leu | missense_variant | 2/8 | 5 | NM_001136239.4 | P1 | |
PRDM6-AS1 | ENST00000458103.2 | n.47G>A | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000529 AC: 8AN: 151234Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000120 AC: 11AN: 91350Hom.: 1 AF XY: 0.0000780 AC XY: 4AN XY: 51260
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GnomAD4 exome AF: 0.0000479 AC: 64AN: 1335506Hom.: 1 Cov.: 44 AF XY: 0.0000395 AC XY: 26AN XY: 658374
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GnomAD4 genome AF: 0.0000529 AC: 8AN: 151340Hom.: 0 Cov.: 33 AF XY: 0.0000541 AC XY: 4AN XY: 73984
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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 | Feb 17, 2024 | The c.239C>T (p.S80L) alteration is located in exon 2 (coding exon 1) of the PRDM6 gene. This alteration results from a C to T substitution at nucleotide position 239, causing the serine (S) at amino acid position 80 to be replaced by a leucine (L). 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Loss of phosphorylation at S80 (P = 0.0013);
MVP
ClinPred
T
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at