rs11654436

Positions:

• chr17-44316094-A-C
• chr17-44316094-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144825.2(RUNDC3A):​c.954-291A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,546 control chromosomes in the GnomAD database, including 24,086 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 0.54 (24086 hom., cov: 29)
• Consequence: RUNDC3A NM_001144825.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUNDC3A	NM_001144825.2	c.954-291A>C		intron_variant		ENST00000426726.8	NP_001138297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNDC3A	ENST00000426726.8	c.954-291A>C		intron_variant		1	NM_001144825.2	ENSP00000410862.2

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81280 AN: 151428 Hom.: 24026 Cov.: 29

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.502

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.537 AC: 81406 AN: 151546 Hom.: 24086 Cov.: 29 AF XY: 0.547 AC XY: 40526 AN XY: 74032

Gnomad4 AFR AF: 0.749

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.508

Alfa AF: 0.451 Hom.: 5201

Bravo AF: 0.554

Asia WGS AF: 0.790 AC: 2745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.2
DANN	Benign	0.74

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

Other links and lift over

dbSNP: rs11654436; hg19: chr17-42393462;