dbSNP rs1273398453: RUNDC1:p.Leu175Gln (chr17-42987281-T-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_173079.5(RUNDC1):c.524T>A(p.Leu175Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. L175P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RUNDC1
NM_173079.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.29

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30097103).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
RUNDC1	NM_173079.5 link	c.524T>A	p.Leu175Gln	missense_variant	Exon 2 of 5	ENST00000361677.6	NP_775102.3
RUNDC1	NM_001321381.3 link	c.530T>A	p.Leu177Gln	missense_variant	Exon 3 of 6		NP_001308310.2
RUNDC1	NM_001394222.1 link	c.524T>A	p.Leu175Gln	missense_variant	Exon 2 of 5		NP_001381151.1
RUNDC1	XM_005257078.5 link	c.530T>A	p.Leu177Gln	missense_variant	Exon 3 of 6		XP_005257135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNDC1	ENST00000361677.6 link	c.524T>A	p.Leu175Gln	missense_variant	Exon 2 of 5	1	NM_173079.5	ENSP00000354622.1		Q96C34-1
RUNDC1	ENST00000589705.1 link	c.518T>A	p.Leu173Gln	missense_variant	Exon 2 of 4	5		ENSP00000467953.1		K7EQS2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248948

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111982

Other (OTH)

AF:

0.00

AC:

AN:

60394

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

0.077

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Benign

0.18

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.76

M_CAP

Benign

0.036

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.9

PhyloP100

3.3

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.28

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0040

Polyphen

0.87

Vest4

0.37

MutPred

0.27

Gain of methylation at K171 (P = 0.0485);

MVP

0.88

MPC

0.46

ClinPred

0.90

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.43

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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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rs1273398453

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over