rs758846620

Variant names:

• chr17-44316444-C-A
• rs758846620
• NM_001144825.2:c.1013C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-44316444-C-A
• chr17-44316444-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001144825.2(RUNDC3A):​c.1013C>A​(p.Thr338Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RUNDC3A NM_001144825.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08874154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNDC3A	NM_001144825.2	c.1013C>A	p.Thr338Lys	missense_variant	Exon 9 of 11	ENST00000426726.8	NP_001138297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNDC3A	ENST00000426726.8	c.1013C>A	p.Thr338Lys	missense_variant	Exon 9 of 11	1	NM_001144825.2	ENSP00000410862.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.040	T;.;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.089	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;.;L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.1	N;.;N
REVEL	Benign	0.042
Sift	Benign	0.037	D;.;D
Sift4G	Uncertain	0.045	D;T;T
Polyphen		0.0050	B;B;B
Vest4		0.41
MutPred		0.39		Gain of ubiquitination at T338 (P = 0.0138);.;Gain of ubiquitination at T338 (P = 0.0138);
MVP		0.068
MPC		1.2
ClinPred		0.33	T
GERP RS		2.6
Varity_R		0.13
gMVP		0.38

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: rs758846620; hg19: chr17-42393812;