17-42989530-T-C

Variant names:

• chr17-42989530-T-C
• rs750828455
• NM_173079.5:c.847T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_173079.5(RUNDC1):​c.847T>C​(p.Phe283Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. F283V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RUNDC1 NM_173079.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.83
• Publications: 0 publications found

Genes affected

RUNDC1 (HGNC:25418): (RUN domain containing 1) This gene encodes a protein that contains a RUN (RPIP8, UNC-14 and NESCA) domain and a coiled coil domain. The encoded protein may negatively regulate p53 transcriptional activity. This gene is a potential candidate gene for predisposition to glioma in humans. [provided by RefSeq, May 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.795

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNDC1	NM_173079.5	c.847T>C	p.Phe283Leu	missense_variant	Exon 3 of 5	ENST00000361677.6	NP_775102.3
RUNDC1	NM_001321381.3	c.853T>C	p.Phe285Leu	missense_variant	Exon 4 of 6		NP_001308310.2
RUNDC1	NM_001394222.1	c.847T>C	p.Phe283Leu	missense_variant	Exon 3 of 5		NP_001381151.1
RUNDC1	XM_005257078.5	c.853T>C	p.Phe285Leu	missense_variant	Exon 4 of 6		XP_005257135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNDC1	ENST00000361677.6	c.847T>C	p.Phe283Leu	missense_variant	Exon 3 of 5	1	NM_173079.5	ENSP00000354622.1
RUNDC1	ENST00000589705.1	c.652-787T>C		intron_variant	Intron 2 of 3	5		ENSP00000467953.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.8
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.45		Loss of helix (P = 0.1706);
MVP		0.50
MPC		1.4
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.63
gMVP		0.70

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: rs750828455; hg19: chr17-41141547;