Variant 17-42980892-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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

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:

RUNDC1 (HGNC:):

RUNDC1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.851

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RUNDC1	NM_173079.5 linkuse as main transcript	c.316T>C	p.Phe106Leu	missense_variant	1/5	ENST00000361677.6	NP_775102.3
RUNDC1	NM_001321381.3 linkuse as main transcript	c.316T>C	p.Phe106Leu	missense_variant	1/6		NP_001308310.2
RUNDC1	NM_001394222.1 linkuse as main transcript	c.316T>C	p.Phe106Leu	missense_variant	1/5		NP_001381151.1
RUNDC1	XM_005257078.5 linkuse as main transcript	c.316T>C	p.Phe106Leu	missense_variant	1/6		XP_005257135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RUNDC1	ENST00000361677.6 linkuse as main transcript	c.316T>C	p.Phe106Leu	missense_variant	1/5	1	NM_173079.5	ENSP00000354622.1	Q96C34-1
RUNDC1	ENST00000589705.1 linkuse as main transcript	c.310T>C	p.Phe104Leu	missense_variant	1/4	5		ENSP00000467953.1	K7EQS2
RUNDC1	ENST00000590836.1 linkuse as main transcript	n.328T>C		non_coding_transcript_exon_variant	1/1	6

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.316T>C (p.F106L) alteration is located in exon 1 (coding exon 1) of the RUNDC1 gene. This alteration results from a T to C substitution at nucleotide position 316, causing the phenylalanine (F) at amino acid position 106 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

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over