17-44315254-T-C

Position:

• chr17-44315254-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
RUNDC3A	NM_001144825.2	c.729T>C	p.Asp243Asp	synonymous_variant	7/11	ENST00000426726.8	NP_001138297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNDC3A	ENST00000426726.8	c.729T>C	p.Asp243Asp	synonymous_variant	7/11	1	NM_001144825.2	ENSP00000410862.2

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

GnomAD3 exomes AF: 0.500 AC: 75081 AN: 150142 Hom.: 20624 AF XY: 0.493 AC XY: 39718 AN XY: 80490

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 SAS exome AF: 0.531

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

Gnomad4 AFR exome AF: 0.698

Gnomad4 AMR exome AF: 0.592

Gnomad4 ASJ exome AF: 0.388

Gnomad4 EAS exome AF: 0.872

Gnomad4 SAS exome AF: 0.525

Gnomad4 FIN exome AF: 0.486

Gnomad4 NFE exome AF: 0.360

Gnomad4 OTH exome AF: 0.444

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

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.478

Alfa AF: 0.392 Hom.: 14648

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	19
DANN	Benign	0.76

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

LitVar

Other links and lift over

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