Genetic Variant RUNDC1:p.Pro72Arg (chr17-42980791-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.215C>G(p.Pro72Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000008 in 1,250,134 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P72L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

RUNDC1
NM_173079.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.28

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=0.14648518).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
RUNDC1	NM_173079.5 link	c.215C>G	p.Pro72Arg	missense_variant	Exon 1 of 5	ENST00000361677.6	NP_775102.3
RUNDC1	NM_001321381.3 link	c.215C>G	p.Pro72Arg	missense_variant	Exon 1 of 6		NP_001308310.2
RUNDC1	NM_001394222.1 link	c.215C>G	p.Pro72Arg	missense_variant	Exon 1 of 5		NP_001381151.1
RUNDC1	XM_005257078.5 link	c.215C>G	p.Pro72Arg	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.215C>G	p.Pro72Arg	missense_variant	Exon 1 of 5	1	NM_173079.5	ENSP00000354622.1	Q96C34-1
RUNDC1	ENST00000589705.1 link	c.209C>G	p.Pro70Arg	missense_variant	Exon 1 of 4	5		ENSP00000467953.1	K7EQS2
RUNDC1	ENST00000590836.1 link	n.227C>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.00e-7

AC:

AN:

1250134

Hom.:

Cov.:

AF XY:

0.00000164

AC XY:

AN XY:

611058

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24382

American (AMR)

AF:

0.0000771

AC:

AN:

12962

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18006

East Asian (EAS)

AF:

0.00

AC:

AN:

27854

South Asian (SAS)

AF:

0.00

AC:

AN:

58784

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3554

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1021616

Other (OTH)

AF:

0.00

AC:

AN:

51532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0081

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.65

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

1.3

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.27

REVEL

Benign

0.055

Sift

Benign

0.28

Sift4G

Benign

0.26

Polyphen

0.45

Vest4

0.34

MutPred

0.17

Gain of MoRF binding (P = 0.0175);

MVP

0.28

MPC

1.3

ClinPred

0.74

GERP RS

4.7

PromoterAI

0.11

Neutral

(source)

Varity_R

0.058

gMVP

0.17

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

Computational scores

Splicing

Publications

Other links and lift over