chr17-44315543-C-T

Variant names:

• chr17-44315543-C-T
• rs550791513
• NM_001144825.2:c.887C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001144825.2(RUNDC3A):​c.887C>T​(p.Ala296Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000132 in 1,515,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: RUNDC3A NM_001144825.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059899718).

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>T	p.Ala296Val	missense	Exon 8 of 11	NP_001138297.1	Q59EK9-1
	RUNDC3A	NM_006695.5		c.887C>T	p.Ala296Val	missense	Exon 8 of 11	NP_006686.1	Q59EK9-3
	RUNDC3A	NM_001144826.2		c.872C>T	p.Ala291Val	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>T	p.Ala296Val	missense	Exon 8 of 11	ENSP00000410862.2	Q59EK9-1
	RUNDC3A	ENST00000225441.11	TSL:1	c.887C>T	p.Ala296Val	missense	Exon 8 of 11	ENSP00000225441.7	Q59EK9-3
	RUNDC3A	ENST00000590941.5	TSL:1	c.872C>T	p.Ala291Val	missense	Exon 8 of 11	ENSP00000468214.1	Q59EK9-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152140 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000887 AC: 1 AN: 112744 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000252

Gnomad OTH exome 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: 9.40e-7 AC: 1 AN: 1064074

Other (OTH) AF: 0.00 AC: 0 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: 0.00000657 AC: 1 AN: 152246 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74422

African (AFR) AF: 0.0000241 AC: 1 AN: 41554

American (AMR) AF: 0.00 AC: 0 AN: 15294

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2112

ExAC AF: 0.0000357 AC: 3

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	0.076
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.060
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.1
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.090
Sift	Benign	0.44	T
Sift4G	Benign	0.44	T
Polyphen		0.27	B
Vest4		0.22
MutPred		0.30		Gain of helix (P = 0.0164)
MVP		0.14
MPC		1.0
ClinPred		0.19	T
GERP RS		4.0
Varity_R		0.080
gMVP		0.20

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;