chr17-42990326-G-C

Position:

• chr17-42990326-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173079.5(RUNDC1):​c.866G>C​(p.Gly289Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RUNDC1 NM_173079.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 6.24

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26417702).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUNDC1	NM_173079.5	c.866G>C	p.Gly289Ala	missense_variant	4/5	ENST00000361677.6	NP_775102.3
RUNDC1	NM_001321381.3	c.872G>C	p.Gly291Ala	missense_variant	5/6		NP_001308310.2
RUNDC1	NM_001394222.1	c.866G>C	p.Gly289Ala	missense_variant	4/5		NP_001381151.1
RUNDC1	XM_005257078.5	c.872G>C	p.Gly291Ala	missense_variant	5/6		XP_005257135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNDC1	ENST00000361677.6	c.866G>C	p.Gly289Ala	missense_variant	4/5	1	NM_173079.5	ENSP00000354622.1
RUNDC1	ENST00000589705.1	c.661G>C	p.Glu221Gln	missense_variant	3/4	5		ENSP00000467953.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

research

Prostate Cancer Research Center, Institute of Biosciences and Medical Technology, University of Tampere

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.080
Sift	Benign	0.076	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.40
MutPred		0.24		Loss of relative solvent accessibility (P = 0.0306);
MVP		0.33
MPC		0.82
ClinPred		0.76	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.077
gMVP		0.34

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

Other links and lift over

dbSNP: rs864622034; hg19: chr17-41142343; COSMIC: COSV64511507;