rs373613588

Variant names:

• chr17-44313119-G-A
• rs373613588
• NM_001144825.2:c.239G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-44313119-G-A
• chr17-44313119-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001144825.2(RUNDC3A):​c.239G>A​(p.Gly80Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RUNDC3A NM_001144825.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.51

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.776

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNDC3A	NM_001144825.2	c.239G>A	p.Gly80Asp	missense_variant	Exon 3 of 11	ENST00000426726.8	NP_001138297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNDC3A	ENST00000426726.8	c.239G>A	p.Gly80Asp	missense_variant	Exon 3 of 11	1	NM_001144825.2	ENSP00000410862.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248914 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135152

Gnomad AFR exome AF: 0.0000647

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461660 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727108

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.77	T;D;T
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Benign	-1.1	T
PrimateAI	Pathogenic	0.80	D
PROVEAN	Uncertain	-3.7	D;.;D
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D;.;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.68
MutPred		0.49		Gain of helix (P = 0.0425);.;Gain of helix (P = 0.0425);
MVP		0.27
MPC		2.4
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.88
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs373613588; hg19: chr17-42390487;