17-44313144-C-G

Variant names:

• chr17-44313144-C-G
• rs773444404
• NM_001144825.2:c.264C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001144825.2(RUNDC3A):​c.264C>G​(p.Asp88Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D88D) has been classified as Likely benign.

• 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: -1.69
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13637865).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144825.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNDC3A	NM_001144825.2	MANE Select	c.264C>G	p.Asp88Glu	missense	Exon 3 of 11	NP_001138297.1	Q59EK9-1
	RUNDC3A	NM_006695.5		c.264C>G	p.Asp88Glu	missense	Exon 3 of 11	NP_006686.1	Q59EK9-3
	RUNDC3A	NM_001144826.2		c.249C>G	p.Asp83Glu	missense	Exon 3 of 11	NP_001138298.1	Q59EK9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNDC3A	ENST00000426726.8	TSL:1 MANE Select	c.264C>G	p.Asp88Glu	missense	Exon 3 of 11	ENSP00000410862.2	Q59EK9-1
	RUNDC3A	ENST00000225441.11	TSL:1	c.264C>G	p.Asp88Glu	missense	Exon 3 of 11	ENSP00000225441.7	Q59EK9-3
	RUNDC3A	ENST00000590941.5	TSL:1	c.249C>G	p.Asp83Glu	missense	Exon 3 of 11	ENSP00000468214.1	Q59EK9-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461704 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727130

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111868

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.5
DANN	Benign	0.97
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.0	L
PhyloP100		-1.7
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.56	N
REVEL	Uncertain	0.33
Sift	Benign	0.91	T
Sift4G	Benign	0.90	T
Polyphen		1.0	D
Vest4		0.17
MutPred		0.33		Gain of MoRF binding (P = 0.1535)
MVP		0.25
MPC		2.1
ClinPred		0.49	T
GERP RS		-7.9
Varity_R		0.15
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs773444404; hg19: chr17-42390512;