Genetic Variant NM_173079.5:c.232C>G (chr17-42980808-C-G) – 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.232C>G(p.Arg78Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000814 in 1,228,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. R78Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 8.1e-7 ( 0 hom. )

Consequence

RUNDC1
NM_173079.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.578

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=0.14311919).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
RUNDC1	NM_173079.5 link	c.232C>G	p.Arg78Gly	missense_variant	Exon 1 of 5	ENST00000361677.6	NP_775102.3
RUNDC1	NM_001321381.3 link	c.232C>G	p.Arg78Gly	missense_variant	Exon 1 of 6		NP_001308310.2
RUNDC1	NM_001394222.1 link	c.232C>G	p.Arg78Gly	missense_variant	Exon 1 of 5		NP_001381151.1
RUNDC1	XM_005257078.5 link	c.232C>G	p.Arg78Gly	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.232C>G	p.Arg78Gly	missense_variant	Exon 1 of 5	1	NM_173079.5	ENSP00000354622.1	Q96C34-1
RUNDC1	ENST00000589705.1 link	c.226C>G	p.Arg76Gly	missense_variant	Exon 1 of 4	5		ENSP00000467953.1	K7EQS2
RUNDC1	ENST00000590836.1 link	n.244C>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.14e-7

AC:

AN:

1228336

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

598994

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23868

American (AMR)

AF:

0.00

AC:

AN:

10390

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16888

East Asian (EAS)

AF:

0.00

AC:

AN:

27594

South Asian (SAS)

AF:

0.00

AC:

AN:

54320

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30236

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3452

European-Non Finnish (NFE)

AF:

9.89e-7

AC:

AN:

1011000

Other (OTH)

AF:

0.00

AC:

AN:

50588

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Sep 05, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.232C>G (p.R78G) alteration is located in exon 1 (coding exon 1) of the RUNDC1 gene. This alteration results from a C to G substitution at nucleotide position 232, causing the arginine (R) at amino acid position 78 to be replaced by a glycine (G). 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

0.076

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.67

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

0.58

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.3

REVEL

Benign

0.055

Sift

Uncertain

0.028

Sift4G

Uncertain

0.048

Polyphen

0.0020

Vest4

0.067

MutPred

0.14

Gain of loop (P = 0.0166);

MVP

0.28

MPC

0.53

ClinPred

0.37

GERP RS

2.9

PromoterAI

-0.12

Neutral

(source)

Varity_R

0.10

gMVP

0.11

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