17-42980645-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173079.5(RUNDC1):​c.69C>A​(p.Asp23Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RUNDC1
NM_173079.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.242
Variant links:
Genes affected
RUNDC1 (HGNC:25418): (RUN domain containing 1) This gene encodes a protein that contains a RUN (RPIP8, UNC-14 and NESCA) domain and a coiled coil domain. The encoded protein may negatively regulate p53 transcriptional activity. This gene is a potential candidate gene for predisposition to glioma in humans. [provided by RefSeq, May 2017]
PTGES3L-AARSD1 (HGNC:43946): (PTGES3L-AARSD1 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring PTGES3L (prostaglandin E synthase 3 (cytosolic)-like) and AARSD1(alanyl-tRNA synthetase domain containing 1) genes on chromosome 17. The readthrough transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, May 2012]
PTGES3L (HGNC:43943): (prostaglandin E synthase 3 like) Predicted to enable Hsp90 protein binding activity and chaperone binding activity. Predicted to be involved in chaperone-mediated protein complex assembly and protein folding. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06928614).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RUNDC1NM_173079.5 linkc.69C>A p.Asp23Glu missense_variant Exon 1 of 5 ENST00000361677.6 NP_775102.3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RUNDC1ENST00000361677.6 linkc.69C>A p.Asp23Glu missense_variant Exon 1 of 5 1 NM_173079.5 ENSP00000354622.1 Q96C34-1
PTGES3L-AARSD1ENST00000421990.7 linkc.-592G>T upstream_gene_variant 2 ENSP00000409924.2 B3KSP9

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
6.90e-7
AC:
1
AN:
1449542
Hom.:
0
Cov.:
75
AF XY:
0.00
AC XY:
0
AN XY:
720390
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.02e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 26, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.69C>A (p.D23E) alteration is located in exon 1 (coding exon 1) of the RUNDC1 gene. This alteration results from a C to A substitution at nucleotide position 69, causing the aspartic acid (D) at amino acid position 23 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
13
DANN
Benign
0.75
DEOGEN2
Benign
0.0096
T
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.52
FATHMM_MKL
Benign
0.031
N
LIST_S2
Benign
0.54
T
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.069
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.41
N
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-0.34
N
REVEL
Benign
0.13
Sift
Benign
0.31
T
Sift4G
Benign
0.35
T
Polyphen
0.012
B
Vest4
0.090
MutPred
0.15
Gain of helix (P = 0.0854);
MVP
0.45
MPC
0.39
ClinPred
0.21
T
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.072
gMVP
0.053

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: chr17-41132662; API