Genetic Variant RUNDC1:p.Arg162Leu (chr17-42981061-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173079.5(RUNDC1):c.485G>T(p.Arg162Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,410,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

RUNDC1
NM_173079.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.45

Publications

0 publications found

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]

RUNDC1 links:

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ACMG classification

Classification was made for transcript

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=0.114151984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
RUNDC1	NM_173079.5 link	c.485G>T	p.Arg162Leu	missense_variant	Exon 1 of 5	ENST00000361677.6	NP_775102.3
RUNDC1	NM_001321381.3 link	c.485G>T	p.Arg162Leu	missense_variant	Exon 1 of 6		NP_001308310.2
RUNDC1	NM_001394222.1 link	c.485G>T	p.Arg162Leu	missense_variant	Exon 1 of 5		NP_001381151.1
RUNDC1	XM_005257078.5 link	c.485G>T	p.Arg162Leu	missense_variant	Exon 1 of 6		XP_005257135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RUNDC1	ENST00000361677.6 link	c.485G>T	p.Arg162Leu	missense_variant	Exon 1 of 5	1	NM_173079.5	ENSP00000354622.1	Q96C34-1
RUNDC1	ENST00000589705.1 link	c.479G>T	p.Arg160Leu	missense_variant	Exon 1 of 4	5		ENSP00000467953.1	K7EQS2
RUNDC1	ENST00000590836.1 link	n.497G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.09e-7

AC:

AN:

1410952

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

700138

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31502

American (AMR)

AF:

0.00

AC:

AN:

40542

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25104

East Asian (EAS)

AF:

0.00

AC:

AN:

36180

South Asian (SAS)

AF:

0.00

AC:

AN:

82014

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36454

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

9.14e-7

AC:

AN:

1094558

Other (OTH)

AF:

0.00

AC:

AN:

58896

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 28, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.485G>T (p.R162L) alteration is located in exon 1 (coding exon 1) of the RUNDC1 gene. This alteration results from a G to T substitution at nucleotide position 485, causing the arginine (R) at amino acid position 162 to be replaced by a leucine (L). 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

0.088

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0089

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.80

M_CAP

Benign

0.070

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

2.4

PrimateAI

Benign

0.43

PROVEAN

Benign

0.53

REVEL

Benign

0.089

Sift

Benign

0.69

Sift4G

Benign

0.72

Polyphen

0.0

Vest4

0.21

MutPred

0.21

Loss of solvent accessibility (P = 0.0606);

MVP

0.60

MPC

0.52

ClinPred

0.26

GERP RS

3.7

PromoterAI

0.023

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.23

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over