rs768598870

Variant names:

• chr17-44312636-C-T
• rs768598870
• NM_001144825.2:c.164C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-44312636-C-T
• chr17-44312636-C-A

Variant summary

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

The NM_001144825.2(RUNDC3A):​c.164C>T​(p.Ser55Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000227 in 1,587,630 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: RUNDC3A NM_001144825.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.81
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.164C>T	p.Ser55Leu	missense	Exon 2 of 11	NP_001138297.1	Q59EK9-1
	RUNDC3A	NM_006695.5		c.164C>T	p.Ser55Leu	missense	Exon 2 of 11	NP_006686.1	Q59EK9-3
	RUNDC3A	NM_001144826.2		c.164C>T	p.Ser55Leu	missense	Exon 2 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.164C>T	p.Ser55Leu	missense	Exon 2 of 11	ENSP00000410862.2	Q59EK9-1
	RUNDC3A	ENST00000225441.11	TSL:1	c.164C>T	p.Ser55Leu	missense	Exon 2 of 11	ENSP00000225441.7	Q59EK9-3
	RUNDC3A	ENST00000590941.5	TSL:1	c.164C>T	p.Ser55Leu	missense	Exon 2 of 11	ENSP00000468214.1	Q59EK9-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152138 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000240 AC: 5 AN: 207918 AF XY: 0.0000179

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000651

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000328

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000244 AC: 35 AN: 1435492 Hom.: 0 Cov.: 31 AF XY: 0.0000211 AC XY: 15 AN XY: 711388

African (AFR) AF: 0.00 AC: 0 AN: 32846

American (AMR) AF: 0.00 AC: 0 AN: 40740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25542

East Asian (EAS) AF: 0.0000260 AC: 1 AN: 38494

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 81818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.0000300 AC: 33 AN: 1099390

Other (OTH) AF: 0.00 AC: 0 AN: 59424

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152138 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74324

African (AFR) AF: 0.00 AC: 0 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

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

Alfa AF: 0.0000197 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000166 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.0015	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.8
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.25
Sift	Benign	0.10	T
Sift4G	Uncertain	0.0020	D
Polyphen		0.98	D
Vest4		0.82
MutPred		0.37		Loss of disorder (P = 0.0048)
MVP		0.082
MPC		1.8
ClinPred		0.71	D
GERP RS		4.1
Varity_R		0.31
gMVP		0.68
Mutation Taster		=62/38	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: rs768598870; hg19: chr17-42390004; COSMIC: COSV56637548; COSMIC: COSV56637548;