17-44315584-G-A

Variant names:

• chr17-44315584-G-A
• rs1482173695
• NM_001144825.2:c.928G>A

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.928G>A​(p.Val310Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000737 in 1,356,818 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V310E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: RUNDC3A NM_001144825.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.55
• 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=0.19549361).

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.928G>A	p.Val310Met	missense	Exon 8 of 11	NP_001138297.1	Q59EK9-1
	RUNDC3A	NM_006695.5		c.928G>A	p.Val310Met	missense	Exon 8 of 11	NP_006686.1	Q59EK9-3
	RUNDC3A	NM_001144826.2		c.913G>A	p.Val305Met	missense	Exon 8 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.928G>A	p.Val310Met	missense	Exon 8 of 11	ENSP00000410862.2	Q59EK9-1
	RUNDC3A	ENST00000225441.11	TSL:1	c.928G>A	p.Val310Met	missense	Exon 8 of 11	ENSP00000225441.7	Q59EK9-3
	RUNDC3A	ENST00000590941.5	TSL:1	c.913G>A	p.Val305Met	missense	Exon 8 of 11	ENSP00000468214.1	Q59EK9-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.37e-7 AC: 1 AN: 1356818 Hom.: 0 Cov.: 33 AF XY: 0.00000150 AC XY: 1 AN XY: 668850

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28528

American (AMR) AF: 0.00 AC: 0 AN: 30834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24146

East Asian (EAS) AF: 0.00 AC: 0 AN: 30406

South Asian (SAS) AF: 0.00 AC: 0 AN: 74984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3954

European-Non Finnish (NFE) AF: 9.43e-7 AC: 1 AN: 1060478

Other (OTH) AF: 0.00 AC: 0 AN: 56088

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Benign	0.0062
Eigen_PC	Benign	0.046
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.5
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.050
Sift	Benign	0.092	T
Sift4G	Uncertain	0.0060	D
Polyphen		0.90	P
Vest4		0.29
MutPred		0.22		Gain of disorder (P = 0.1341)
MVP		0.13
MPC		1.9
ClinPred		0.80	D
GERP RS		3.0
Varity_R		0.095
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1482173695; hg19: chr17-42392952;