chr17-42990352-C-T

Variant names:

• chr17-42990352-C-T
• rs747514103
• NM_173079.5:c.892C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173079.5(RUNDC1):​c.892C>T​(p.His298Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: RUNDC1 NM_173079.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.14
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15234536).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173079.5. 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
	RUNDC1	NM_173079.5	MANE Select	c.892C>T	p.His298Tyr	missense	Exon 4 of 5	NP_775102.3	Q96C34-1
	RUNDC1	NM_001321381.3		c.898C>T	p.His300Tyr	missense	Exon 5 of 6	NP_001308310.2
	RUNDC1	NM_001394222.1		c.892C>T	p.His298Tyr	missense	Exon 4 of 5	NP_001381151.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNDC1	ENST00000361677.6	TSL:1 MANE Select	c.892C>T	p.His298Tyr	missense	Exon 4 of 5	ENSP00000354622.1	Q96C34-1
	RUNDC1	ENST00000903300.1		c.892C>T	p.His298Tyr	missense	Exon 4 of 5	ENSP00000573359.1
	RUNDC1	ENST00000903301.1		c.733C>T	p.His245Tyr	missense	Exon 3 of 4	ENSP00000573360.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251270 AF XY: 0.00000736

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: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461778 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727176

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111984

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.087
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	22
DANN	Benign	0.88
DEOGEN2	Benign	0.023	T
Eigen	Benign	0.011
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.1
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.027
Sift	Benign	0.20	T
Sift4G	Benign	0.10	T
Polyphen		0.10	B
Vest4		0.31
MutPred		0.23		Loss of disorder (P = 0.0674)
MVP		0.21
MPC		0.55
ClinPred		0.32	T
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.095
gMVP		0.14
Mutation Taster		=98/2	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: rs747514103; hg19: chr17-41142369;