chr1-30933257-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001020658.2(PUM1):​c.3521G>T​(p.Gly1174Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

PUM1
NM_001020658.2 missense

Scores

4
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.90
Variant links:
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PUM1NM_001020658.2 linkc.3521G>T p.Gly1174Val missense_variant Exon 22 of 22 ENST00000426105.7 NP_001018494.1 Q14671-3
PUM1NM_014676.3 linkc.3515G>T p.Gly1172Val missense_variant Exon 22 of 22 NP_055491.1 Q14671-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PUM1ENST00000426105.7 linkc.3521G>T p.Gly1174Val missense_variant Exon 22 of 22 1 NM_001020658.2 ENSP00000391723.2 Q14671-3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Sep 05, 2024
GeneDx
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.43
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.070
CADD
Uncertain
24
DANN
Benign
0.97
DEOGEN2
Benign
0.064
T;T;.;.;.;.;.
Eigen
Benign
0.15
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.97
D;D;D;D;D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Uncertain
0.44
T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
.;L;.;.;.;.;.
PrimateAI
Pathogenic
0.79
T
PROVEAN
Uncertain
-2.8
D;D;D;D;D;D;D
REVEL
Uncertain
0.32
Sift
Pathogenic
0.0
D;D;D;D;D;D;D
Sift4G
Uncertain
0.030
D;D;D;D;D;D;D
Polyphen
0.013, 0.14, 0.22, 0.016
.;B;B;.;B;B;.
Vest4
0.58
MutPred
0.49
.;.;.;.;.;Loss of ubiquitination at K1208 (P = 0.045);.;
MVP
0.51
MPC
1.2
ClinPred
0.97
D
GERP RS
5.0
Varity_R
0.60
gMVP
0.83

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1639030753; hg19: chr1-31406104; API