5-123180296-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001136239.4(PRDM6):​c.1646G>T​(p.Arg549Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

PRDM6
NM_001136239.4 missense

Scores

9
5
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.60
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.869

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRDM6NM_001136239.4 linkc.1646G>T p.Arg549Leu missense_variant Exon 7 of 8 ENST00000407847.5 NP_001129711.1 Q9NQX0-3
PRDM6XM_011543726.4 linkc.1046G>T p.Arg349Leu missense_variant Exon 6 of 7 XP_011542028.1
PRDM6XR_001742346.2 linkn.1940G>T non_coding_transcript_exon_variant Exon 7 of 9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRDM6ENST00000407847.5 linkc.1646G>T p.Arg549Leu missense_variant Exon 7 of 8 5 NM_001136239.4 ENSP00000384725.3 Q9NQX0-3
PRDM6ENST00000427739.1 linkn.233G>T non_coding_transcript_exon_variant Exon 2 of 2 3
PRDM6ENST00000434521.1 linkn.*490G>T downstream_gene_variant 2 ENSP00000390919.1 H7BZR2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.090
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Benign
0.062
T
Eigen
Pathogenic
0.85
Eigen_PC
Pathogenic
0.89
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.075
D
MetaRNN
Pathogenic
0.87
D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L
PrimateAI
Pathogenic
0.95
D
PROVEAN
Pathogenic
-6.1
D
REVEL
Uncertain
0.56
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.017
D
Polyphen
1.0
D
Vest4
0.83
MutPred
0.77
Loss of disorder (P = 0.0354);
MVP
0.57
ClinPred
1.0
D
GERP RS
6.1
Varity_R
0.72
gMVP
0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-122515990; API