Variant 17-44316631-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001144825.2(RUNDC3A):c.1104G>A(p.Met368Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,551,304 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0093 ( 6 hom., cov: 31)

Exomes 𝑓: 0.012 ( 117 hom. )

Consequence

RUNDC3A
NM_001144825.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.29

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004394144).

BP6

Variant 17-44316631-G-A is Benign according to our data. Variant chr17-44316631-G-A is described in ClinVar as [Benign]. Clinvar id is 2647831.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUNDC3A	NM_001144825.2 linkuse as main transcript	c.1104G>A	p.Met368Ile	missense_variant	10/11	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.1104G>A	p.Met368Ile	missense_variant	10/11	1	NM_001144825.2	ENSP00000410862	P1	Q59EK9-1

Frequencies

GnomAD3 genomes

AF:

0.00928

AC:

1411

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.00831

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00599

Gnomad FIN

AF:

0.0145

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0140

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.00896

AC:

1383

AN:

154342

Hom.:

AF XY:

0.00902

AC XY:

743

AN XY:

82338

show subpopulations

Gnomad AFR exome

AF:

0.00119

Gnomad AMR exome

AF:

0.00473

Gnomad ASJ exome

AF:

0.00829

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00573

Gnomad FIN exome

AF:

0.0138

Gnomad NFE exome

AF:

0.0131

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

AF:

0.0117

AC:

16320

AN:

1399076

Hom.:

117

Cov.:

AF XY:

0.0115

AC XY:

7964

AN XY:

690134

show subpopulations

Gnomad4 AFR exome

AF:

0.00145

Gnomad4 AMR exome

AF:

0.00389

Gnomad4 ASJ exome

AF:

0.00711

Gnomad4 EAS exome

AF:

0.0000559

Gnomad4 SAS exome

AF:

0.00585

Gnomad4 FIN exome

AF:

0.0154

Gnomad4 NFE exome

AF:

0.0130

Gnomad4 OTH exome

AF:

0.0106

GnomAD4 genome

AF:

0.00926

AC:

1410

AN:

152228

Hom.:

Cov.:

AF XY:

0.00916

AC XY:

682

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00222

Gnomad4 AMR

AF:

0.00830

Gnomad4 ASJ

AF:

0.00950

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00600

Gnomad4 FIN

AF:

0.0145

Gnomad4 NFE

AF:

0.0140

Gnomad4 OTH

AF:

0.00617

Alfa

AF:

0.0126

Hom.:

Bravo

AF:

0.00803

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.0132

AC:

ESP6500AA

AF:

0.00261

AC:

ESP6500EA

AF:

0.0123

AC:

100

ExAC

AF:

0.00546

AC:

526

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

RUNDC3A: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.047

T;.;.

Eigen

Benign

-0.19

Eigen_PC

Benign

0.056

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.94

D;D;D

MetaRNN

Benign

0.0044

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;N

MutationTaster

Benign

0.89

D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.2

N;.;N

REVEL

Benign

0.075

Sift

Benign

0.35

T;.;T

Sift4G

Benign

0.47

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.32

MutPred

0.18

Gain of sheet (P = 0.0477);.;Gain of sheet (P = 0.0477);

MVP

0.13

MPC

1.1

ClinPred

0.0089

GERP RS

5.6

Varity_R

0.27

gMVP

0.20

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