Genetic Variant NM_001144825.2:c.729T>C (chr17-44315254-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001144825.2(RUNDC3A):c.729T>C(p.Asp243Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 1,550,050 control chromosomes in the GnomAD database, including 144,365 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.50 ( 21167 hom., cov: 33)

Exomes 𝑓: 0.40 ( 123198 hom. )

Consequence

RUNDC3A
NM_001144825.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.396

Publications

19 publications found

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:

RUNDC3A-AS1 (HGNC:51344): (RUNDC3A antisense RNA 1)

RUNDC3A-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP7

Synonymous conserved (PhyloP=-0.396 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNDC3A	NM_001144825.2 link	c.729T>C	p.Asp243Asp	synonymous_variant	Exon 7 of 11	ENST00000426726.8	NP_001138297.1	Q59EK9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNDC3A	ENST00000426726.8 link	c.729T>C	p.Asp243Asp	synonymous_variant	Exon 7 of 11	1	NM_001144825.2	ENSP00000410862.2		Q59EK9-1

Frequencies

GnomAD3 genomes

AF:

0.504

AC:

76662

AN:

151982

Hom.:

21119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.680

Gnomad AMI

AF:

0.409

Gnomad AMR

AF:

0.535

Gnomad ASJ

AF:

0.397

Gnomad EAS

AF:

0.898

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.492

Gnomad MID

AF:

0.369

Gnomad NFE

AF:

0.367

Gnomad OTH

AF:

0.472

GnomAD2 exomes

AF:

0.500

AC:

75081

AN:

150142

AF XY:

0.493

show subpopulations

Gnomad AFR exome

AF:

0.686

Gnomad AMR exome

AF:

0.601

Gnomad ASJ exome

AF:

0.384

Gnomad EAS exome

AF:

0.906

Gnomad FIN exome

AF:

0.490

Gnomad NFE exome

AF:

0.363

Gnomad OTH exome

AF:

0.466

GnomAD4 exome

AF:

0.405

AC:

565975

AN:

1397950

Hom.:

123198

Cov.:

AF XY:

0.407

AC XY:

280337

AN XY:

689564

show subpopulations

African (AFR)

AF:

0.698

AC:

22041

AN:

31576

American (AMR)

AF:

0.592

AC:

21126

AN:

35674

Ashkenazi Jewish (ASJ)

AF:

0.388

AC:

9757

AN:

25144

East Asian (EAS)

AF:

0.872

AC:

31144

AN:

35712

South Asian (SAS)

AF:

0.525

AC:

41700

AN:

79408

European-Finnish (FIN)

AF:

0.486

AC:

23445

AN:

48198

Middle Eastern (MID)

AF:

0.400

AC:

2270

AN:

5676

European-Non Finnish (NFE)

AF:

0.360

AC:

388752

AN:

1078608

Other (OTH)

AF:

0.444

AC:

25740

AN:

57954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

17395

34790

52186

69581

86976

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.505

AC:

76773

AN:

152100

Hom.:

21167

Cov.:

AF XY:

0.515

AC XY:

38304

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.681

AC:

28266

AN:

41530

American (AMR)

AF:

0.536

AC:

8200

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.397

AC:

1377

AN:

3468

East Asian (EAS)

AF:

0.898

AC:

4632

AN:

5158

South Asian (SAS)

AF:

0.550

AC:

2651

AN:

4824

European-Finnish (FIN)

AF:

0.492

AC:

5204

AN:

10580

Middle Eastern (MID)

AF:

0.366

AC:

107

AN:

292

European-Non Finnish (NFE)

AF:

0.367

AC:

24957

AN:

67934

Other (OTH)

AF:

0.478

AC:

1010

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1872

3743

5615

7486

9358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.413

Hom.:

22186

Bravo

AF:

0.520

Asia WGS

AF:

0.722

AC:

2507

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

-0.40

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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NM_001144825.2:c.729T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over