chr17-44315543-C-A

Variant names:

• chr17-44315543-C-A
• rs550791513
• NM_001144825.2:c.887C>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.887C>A​(p.Ala296Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000022 in 1,363,220 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000022 (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=0.10096678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNDC3A	NM_001144825.2	c.887C>A	p.Ala296Glu	missense_variant	Exon 8 of 11	ENST00000426726.8	NP_001138297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNDC3A	ENST00000426726.8	c.887C>A	p.Ala296Glu	missense_variant	Exon 8 of 11	1	NM_001144825.2	ENSP00000410862.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000220 AC: 3 AN: 1363220 Hom.: 0 Cov.: 33 AF XY: 0.00000298 AC XY: 2 AN XY: 671986

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: 0.0000132 AC: 1 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: 0.00000188 AC: 2 AN: 1064074

Other (OTH) AF: 0.00 AC: 0 AN: 56488

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T;.;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.56	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;.;N
PhyloP100		1.1
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.8	N;.;N
REVEL	Benign	0.10
Sift	Benign	0.15	T;.;T
Sift4G	Benign	0.96	T;T;T
Polyphen		0.14	B;P;P
Vest4		0.36
MutPred		0.25		Gain of solvent accessibility (P = 0.1185);.;Gain of solvent accessibility (P = 0.1185);
MVP		0.093
MPC		1.3
ClinPred		0.55	D
GERP RS		4.0
Varity_R		0.29
gMVP		0.57
Mutation Taster		=85/15	polymorphism

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;