NM_001144825.2:c.729T>C

Variant names:

• chr17-44315254-T-C
• rs708386
• NM_001144825.2:c.729T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.396
• Publications: 19 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144825.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNDC3A	NM_001144825.2	MANE Select	c.729T>C	p.Asp243Asp	synonymous	Exon 7 of 11	NP_001138297.1
	RUNDC3A	NM_006695.5		c.729T>C	p.Asp243Asp	synonymous	Exon 7 of 11	NP_006686.1
	RUNDC3A	NM_001144826.2		c.714T>C	p.Asp238Asp	synonymous	Exon 7 of 11	NP_001138298.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNDC3A	ENST00000426726.8	TSL:1 MANE Select	c.729T>C	p.Asp243Asp	synonymous	Exon 7 of 11	ENSP00000410862.2
	RUNDC3A	ENST00000225441.11	TSL:1	c.729T>C	p.Asp243Asp	synonymous	Exon 7 of 11	ENSP00000225441.7
	RUNDC3A	ENST00000590941.5	TSL:1	c.714T>C	p.Asp238Asp	synonymous	Exon 7 of 11	ENSP00000468214.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76662 AN: 151982 Hom.: 21119 Cov.: 33

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

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.: 51 AF XY: 0.407 AC XY: 280337 AN XY: 689564

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

GnomAD4 genome AF: 0.505 AC: 76773 AN: 152100 Hom.: 21167 Cov.: 33 AF XY: 0.515 AC XY: 38304 AN XY: 74372

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Benign	0.76
PhyloP100		-0.40
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs708386; hg19: chr17-42392622; COSMIC: COSV56589088; COSMIC: COSV56589088;