Genetic Variant RUNDC1:p.Gln103Arg (chr17-42980884-A-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_173079.5(RUNDC1):c.308A>G(p.Gln103Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RUNDC1
NM_173079.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.59

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.897

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
RUNDC1	NM_173079.5 link	c.308A>G	p.Gln103Arg	missense_variant	Exon 1 of 5	ENST00000361677.6	NP_775102.3
RUNDC1	NM_001321381.3 link	c.308A>G	p.Gln103Arg	missense_variant	Exon 1 of 6		NP_001308310.2
RUNDC1	NM_001394222.1 link	c.308A>G	p.Gln103Arg	missense_variant	Exon 1 of 5		NP_001381151.1
RUNDC1	XM_005257078.5 link	c.308A>G	p.Gln103Arg	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.308A>G	p.Gln103Arg	missense_variant	Exon 1 of 5	1	NM_173079.5	ENSP00000354622.1	Q96C34-1
RUNDC1	ENST00000589705.1 link	c.302A>G	p.Gln101Arg	missense_variant	Exon 1 of 4	5		ENSP00000467953.1	K7EQS2
RUNDC1	ENST00000590836.1 link	n.320A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1353816

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

666974

African (AFR)

AF:

0.00

AC:

AN:

28372

American (AMR)

AF:

0.00

AC:

AN:

33062

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23966

East Asian (EAS)

AF:

0.00

AC:

AN:

31842

South Asian (SAS)

AF:

0.00

AC:

AN:

76738

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33304

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4088

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1066032

Other (OTH)

AF:

0.00

AC:

AN:

56412

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

Jun 26, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.308A>G (p.Q103R) alteration is located in exon 1 (coding exon 1) of the RUNDC1 gene. This alteration results from a A to G substitution at nucleotide position 308, causing the glutamine (Q) at amino acid position 103 to be replaced by an arginine (R). 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

Pathogenic

0.65

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.35

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.42

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.95

MetaRNN

Pathogenic

0.90

MetaSVM

Uncertain

0.065

MutationAssessor

Uncertain

2.5

PhyloP100

7.6

PrimateAI

Pathogenic

0.95

PROVEAN

Uncertain

-3.4

REVEL

Pathogenic

0.73

Sift

Uncertain

0.010

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.72

MutPred

0.54

Gain of methylation at Q103 (P = 0.041);

MVP

0.86

MPC

1.1

ClinPred

1.0

GERP RS

5.0

PromoterAI

0.060

Neutral

(source)

Varity_R

0.83

gMVP

0.80

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