chr1-30942012-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001020658.2(PUM1):c.3106G>A(p.Glu1036Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,156 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
PUM1
NM_001020658.2 missense
NM_001020658.2 missense
Scores
4
7
7
Clinical Significance
Conservation
PhyloP100: 7.91
Genes affected
PUM1 (HGNC:14957): (pumilio RNA binding family member 1) This gene encodes a member of the PUF family, evolutionarily conserved RNA-binding proteins related to the Pumilio proteins of Drosophila and the fem-3 mRNA binding factor proteins of C. elegans. The encoded protein contains a sequence-specific RNA binding domain comprised of eight repeats and N- and C-terminal flanking regions, and serves as a translational regulator of specific mRNAs by binding to their 3' untranslated regions. The evolutionarily conserved function of the encoded protein in invertebrates and lower vertebrates suggests that the human protein may be involved in translational regulation of embryogenesis, and cell development and differentiation. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, PUM1
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PUM1 | NM_001020658.2 | c.3106G>A | p.Glu1036Lys | missense_variant | 19/22 | ENST00000426105.7 | |
PUM1 | NM_014676.3 | c.3100G>A | p.Glu1034Lys | missense_variant | 19/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PUM1 | ENST00000426105.7 | c.3106G>A | p.Glu1036Lys | missense_variant | 19/22 | 1 | NM_001020658.2 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD3 genomes
?
Cov.:
30
GnomAD4 exome AF: 7.00e-7 AC: 1AN: 1428156Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1AN XY: 711042
GnomAD4 exome
AF:
AC:
1
AN:
1428156
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
711042
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
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Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 30
GnomAD4 genome
?
Cov.:
30
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 21, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;.;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D;D;D;D
REVEL
Benign
Sift
Benign
T;D;D;D;T;D;D
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
0.017, 0.0070, 0.24, 0.0020
.;B;B;.;B;B;.
Vest4
MutPred
0.51
.;.;.;.;.;Gain of ubiquitination at E1072 (P = 0.0258);.;
MVP
MPC
1.1
ClinPred
D
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