17-42980645-C-G

Variant names:

• chr17-42980645-C-G
• rs2050061779
• NM_173079.5:c.69C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173079.5(RUNDC1):​c.69C>G​(p.Asp23Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: RUNDC1 NM_173079.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06894332).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNDC1	NM_173079.5	c.69C>G	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
RUNDC1	ENST00000361677.6	c.69C>G	p.Asp23Glu	missense_variant	Exon 1 of 5	1	NM_173079.5	ENSP00000354622.1
PTGES3L-AARSD1	ENST00000421990.7	c.-592G>C		upstream_gene_variant		2		ENSP00000409924.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 75

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

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	0.68
DEOGEN2	Benign	0.0096	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.022	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
PhyloP100		0.24
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		0.17	T
GERP RS		3.8
PromoterAI		0.37	Neutral
Varity_R		0.072
gMVP		0.053
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs2050061779; hg19: chr17-41132662;