17-42981055-G-T

Variant names:

Variant summary

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

The NM_173079.5(RUNDC1):c.479G>T(p.Trp160Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000355 in 1,409,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W160R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

RUNDC1
NM_173079.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.24

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:

Genome browser will be placed here

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=0.078353256).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
RUNDC1	NM_173079.5 link	c.479G>T	p.Trp160Leu	missense_variant	Exon 1 of 5	ENST00000361677.6	NP_775102.3
RUNDC1	NM_001321381.3 link	c.479G>T	p.Trp160Leu	missense_variant	Exon 1 of 6		NP_001308310.2
RUNDC1	NM_001394222.1 link	c.479G>T	p.Trp160Leu	missense_variant	Exon 1 of 5		NP_001381151.1
RUNDC1	XM_005257078.5 link	c.479G>T	p.Trp160Leu	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.479G>T	p.Trp160Leu	missense_variant	Exon 1 of 5	1	NM_173079.5	ENSP00000354622.1	Q96C34-1
RUNDC1	ENST00000589705.1 link	c.473G>T	p.Trp158Leu	missense_variant	Exon 1 of 4	5		ENSP00000467953.1	K7EQS2
RUNDC1	ENST00000590836.1 link	n.491G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000580

AC:

AN:

172366

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000130

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000355

AC:

AN:

1409066

Hom.:

Cov.:

AF XY:

0.00000286

AC XY:

AN XY:

698982

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31458

American (AMR)

AF:

0.00

AC:

AN:

40298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25088

East Asian (EAS)

AF:

0.00

AC:

AN:

36086

South Asian (SAS)

AF:

0.00

AC:

AN:

81806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00000457

AC:

AN:

1093432

Other (OTH)

AF:

0.00

AC:

AN:

58788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000261

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 07, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.479G>T (p.R160L) 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 479, causing the arginine (R) at amino acid position 160 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

0.068

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0073

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.22

M_CAP

Benign

0.054

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

PhyloP100

2.2

PrimateAI

Uncertain

0.54

PROVEAN

Benign

1.9

REVEL

Benign

0.091

Sift

Benign

0.38

Sift4G

Benign

0.70

Polyphen

0.0

Vest4

0.23

MutPred

0.24

Loss of catalytic residue at W160 (P = 0.191);

MVP

0.62

MPC

0.73

ClinPred

0.16

GERP RS

3.8

PromoterAI

0.097

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.27

Mutation Taster

=100/0

polymorphism

(source)

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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17-42981055-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over