Genetic Variant RUNDC1:p.Phe106Leu (chr17-42980892-T-C) – 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.316T>C(p.Phe106Leu) variant causes a missense change. 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: 4.99

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, 0.851

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173079.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RUNDC1	NM_173079.5	MANE Select	c.316T>C	p.Phe106Leu	missense	Exon 1 of 5	NP_775102.3	Q96C34-1
RUNDC1	NM_001321381.3		c.316T>C	p.Phe106Leu	missense	Exon 1 of 6	NP_001308310.2
RUNDC1	NM_001394222.1		c.316T>C	p.Phe106Leu	missense	Exon 1 of 5	NP_001381151.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RUNDC1	ENST00000361677.6	TSL:1 MANE Select	c.316T>C	p.Phe106Leu	missense	Exon 1 of 5	ENSP00000354622.1	Q96C34-1
RUNDC1	ENST00000903300.1		c.316T>C	p.Phe106Leu	missense	Exon 1 of 5	ENSP00000573359.1
RUNDC1	ENST00000954068.1		c.316T>C	p.Phe106Leu	missense	Exon 1 of 4	ENSP00000624127.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1371632

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

676560

African (AFR)

AF:

0.00

AC:

AN:

30150

American (AMR)

AF:

0.00

AC:

AN:

35050

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24604

East Asian (EAS)

AF:

0.00

AC:

AN:

34250

South Asian (SAS)

AF:

0.00

AC:

AN:

78392

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33560

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4230

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1074150

Other (OTH)

AF:

0.00

AC:

AN:

57246

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.85

M_CAP

Pathogenic

0.87

MetaRNN

Pathogenic

0.85

MetaSVM

Uncertain

-0.27

MutationAssessor

Benign

1.6

PhyloP100

5.0

PrimateAI

Pathogenic

0.97

PROVEAN

Uncertain

-4.0

REVEL

Uncertain

0.63

Sift

Benign

0.23

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.74

MutPred

0.60

Gain of disorder (P = 0.129)

MVP

0.73

MPC

1.1

ClinPred

1.0

GERP RS

5.0

PromoterAI

-0.16

Neutral

(source)

Varity_R

0.72

gMVP

0.67

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over