chr17-42980791-C-T

Variant names:

• chr17-42980791-C-T
• rs974858698
• NM_173079.5:c.215C>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.215C>T​(p.Pro72Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000008 in 1,250,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: RUNDC1 NM_173079.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28
• 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=0.121907175).

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.215C>T	p.Pro72Leu	missense	Exon 1 of 5	NP_775102.3	Q96C34-1
	RUNDC1	NM_001321381.3		c.215C>T	p.Pro72Leu	missense	Exon 1 of 6	NP_001308310.2
	RUNDC1	NM_001394222.1		c.215C>T	p.Pro72Leu	missense	Exon 1 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.215C>T	p.Pro72Leu	missense	Exon 1 of 5	ENSP00000354622.1	Q96C34-1
	RUNDC1	ENST00000903300.1		c.215C>T	p.Pro72Leu	missense	Exon 1 of 5	ENSP00000573359.1
	RUNDC1	ENST00000954068.1		c.215C>T	p.Pro72Leu	missense	Exon 1 of 4	ENSP00000624127.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 8.00e-7 AC: 1 AN: 1250134 Hom.: 0 Cov.: 75 AF XY: 0.00000164 AC XY: 1 AN XY: 611058

African (AFR) AF: 0.00 AC: 0 AN: 24382

American (AMR) AF: 0.00 AC: 0 AN: 12962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18006

East Asian (EAS) AF: 0.00 AC: 0 AN: 27854

South Asian (SAS) AF: 0.0000170 AC: 1 AN: 58784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3554

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1021616

Other (OTH) AF: 0.00 AC: 0 AN: 51532

GnomAD4 genome Cov.: 34

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	0.075
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0080	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.75	T
M_CAP	Pathogenic	0.37	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.3
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.057
Sift	Benign	0.16	T
Sift4G	Benign	0.20	T
Polyphen		0.27	B
Vest4		0.25
MutPred		0.15		Loss of glycosylation at P72 (P = 0.0179)
MVP		0.29
MPC		1.3
ClinPred		0.90	D
GERP RS		4.7
PromoterAI		0.031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.058
gMVP		0.19

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: rs974858698; hg19: chr17-41132808;