17-44315543-C-G

Variant names:

• chr17-44315543-C-G
• rs550791513
• NM_001144825.2:c.887C>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.887C>G​(p.Ala296Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000198 in 1,515,360 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. A296V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: RUNDC3A NM_001144825.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 1 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=0.11084047).

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.887C>G	p.Ala296Gly	missense	Exon 8 of 11	NP_001138297.1	Q59EK9-1
	RUNDC3A	NM_006695.5		c.887C>G	p.Ala296Gly	missense	Exon 8 of 11	NP_006686.1	Q59EK9-3
	RUNDC3A	NM_001144826.2		c.872C>G	p.Ala291Gly	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.887C>G	p.Ala296Gly	missense	Exon 8 of 11	ENSP00000410862.2	Q59EK9-1
	RUNDC3A	ENST00000225441.11	TSL:1	c.887C>G	p.Ala296Gly	missense	Exon 8 of 11	ENSP00000225441.7	Q59EK9-3
	RUNDC3A	ENST00000590941.5	TSL:1	c.872C>G	p.Ala291Gly	missense	Exon 8 of 11	ENSP00000468214.1	Q59EK9-2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152140 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.34e-7 AC: 1 AN: 1363220 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 671986

⚠️ 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: 28788

American (AMR) AF: 0.00 AC: 0 AN: 31686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24332

East Asian (EAS) AF: 0.00 AC: 0 AN: 30848

South Asian (SAS) AF: 0.00 AC: 0 AN: 75540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4004

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1064074

Other (OTH) AF: 0.0000177 AC: 1 AN: 56488

⚠️ 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 AF: 0.0000131 AC: 2 AN: 152140 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74306

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

African (AFR) AF: 0.0000241 AC: 1 AN: 41438

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000812204), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.0085
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.093
Sift	Benign	0.091	T
Sift4G	Benign	0.42	T
Polyphen		0.25	B
Vest4		0.20
MutPred		0.21		Gain of helix (P = 0.027)
MVP		0.12
MPC		1.2
ClinPred		0.66	D
GERP RS		4.0
Varity_R		0.23
gMVP		0.27

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: rs550791513; hg19: chr17-42392911;