17-42990856-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173079.5(RUNDC1):c.982G>A(p.Ala328Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)
• Consequence: RUNDC1 NM_173079.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.23

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06993675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUNDC1	NM_173079.5	c.982G>A	p.Ala328Thr	missense_variant	5/5	ENST00000361677.6
RUNDC1	NM_001321381.3	c.988G>A	p.Ala330Thr	missense_variant	6/6
RUNDC1	NM_001394222.1	c.985G>A	p.Ala329Thr	missense_variant	5/5
RUNDC1	XM_005257078.5	c.991G>A	p.Ala331Thr	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNDC1	ENST00000361677.6	c.982G>A	p.Ala328Thr	missense_variant	5/5	1	NM_173079.5	P1
RUNDC1	ENST00000589705.1	c.780G>A	p.Arg260=	synonymous_variant	4/4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 01, 2022

The c.982G>A (p.A328T) alteration is located in exon 5 (coding exon 5) of the RUNDC1 gene. This alteration results from a G to A substitution at nucleotide position 982, causing the alanine (A) at amino acid position 328 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	18
Dann	Benign	0.84
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.22
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.026
Sift	Benign	0.56	T
Sift4G	Benign	0.58	T
Polyphen		0.18	B
Vest4		0.040
MutPred		0.28		Gain of phosphorylation at A328 (P = 0.0048);
MVP		0.28
MPC		0.52
ClinPred		0.33	T
GERP RS		1.8
Varity_R		0.020
gMVP		0.17

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-41142873;