chr17-44315254-T-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001144825.2(RUNDC3A):​c.729T>G​(p.Asp243Glu) 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. 14/22 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: 33)
• Consequence: RUNDC3A NM_001144825.2 missense
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27995157).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNDC3A	NM_001144825.2	c.729T>G	p.Asp243Glu	missense_variant	Exon 7 of 11	ENST00000426726.8	NP_001138297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNDC3A	ENST00000426726.8	c.729T>G	p.Asp243Glu	missense_variant	Exon 7 of 11	1	NM_001144825.2	ENSP00000410862.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.063	T;.;.
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.79	N;.;N
PhyloP100		-0.40
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-2.0	N;.;N
REVEL	Benign	0.061
Sift	Benign	0.059	T;.;T
Sift4G	Benign	0.27	T;T;T
Polyphen		0.10	B;B;B
Vest4		0.17
MutPred		0.39		Loss of helix (P = 0.0167);.;Loss of helix (P = 0.0167);
MVP		0.11
MPC		0.94
ClinPred		0.65	D
GERP RS		1.1
Varity_R		0.23
gMVP		0.41

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

Other links and lift over

dbSNP: rs708386; hg19: chr17-42392622;