Variant 17-44316493-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001144825.2(RUNDC3A):c.1062G>C(p.Glu354Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

RUNDC3A
NM_001144825.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.951

Variant links:

Genes affected

RUNDC3A (HGNC:16984): (RUN domain containing 3A) Predicted to enable GTPase regulator activity. Predicted to be involved in positive regulation of cGMP-mediated signaling. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

RUNDC3A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.077771604).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUNDC3A	NM_001144825.2 linkuse as main transcript	c.1062G>C	p.Glu354Asp	missense_variant	9/11	ENST00000426726.8	NP_001138297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNDC3A	ENST00000426726.8 linkuse as main transcript	c.1062G>C	p.Glu354Asp	missense_variant	9/11	1	NM_001144825.2	ENSP00000410862	P1	Q59EK9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000821

AC:

AN:

243586

Hom.:

AF XY:

0.00000750

AC XY:

AN XY:

133294

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad SAS 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:

0.00000411

AC:

AN:

1460382

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726490

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000166

AC:

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

May 17, 2023

The c.1062G>C (p.E354D) alteration is located in exon 9 (coding exon 9) of the RUNDC3A gene. This alteration results from a G to C substitution at nucleotide position 1062, causing the glutamic acid (E) at amino acid position 354 to be replaced by an aspartic acid (D). 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

Benign

0.069

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

T;.;.

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.078

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.;N

MutationTaster

Benign

0.96

D;D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.71

N;.;N

REVEL

Benign

0.039

Sift

Benign

0.29

T;.;T

Sift4G

Benign

0.47

T;T;T

Polyphen

0.0020

B;B;B

Vest4

0.11

MutPred

0.15

Loss of disorder (P = 0.1539);.;Loss of disorder (P = 0.1539);

MVP

0.16

MPC

0.92

ClinPred

0.11

GERP RS

3.7

Varity_R

0.13

gMVP

0.21

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