ENST00000338888.4:c.53T>C

Variant names:

• chr1-24964519-A-G
• rs6672420
• ENST00000338888.4:c.53T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000338888.4(RUNX3):​c.53T>C​(p.Ile18Thr) 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. 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. I18N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RUNX3 ENST00000338888.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.82
• Publications: 61 publications found

Genes affected

RUNX3 (HGNC:10473): (RUNX family transcription factor 3) This gene encodes a member of the runt domain-containing family of transcription factors. A heterodimer of this protein and a beta subunit forms a complex that binds to the core DNA sequence 5'-PYGPYGGT-3' found in a number of enhancers and promoters, and can either activate or suppress transcription. It also interacts with other transcription factors. It functions as a tumor suppressor, and the gene is frequently deleted or transcriptionally silenced in cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

RUNX3-AS1 (HGNC:40513): (RUNX3 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35551846).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000338888.4. 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
	RUNX3	NM_001031680.2		c.53T>C	p.Ile18Thr	missense	Exon 1 of 6	NP_001026850.1	Q13761-2
	RUNX3	NM_001320672.1		c.53T>C	p.Ile18Thr	missense	Exon 2 of 7	NP_001307601.1	Q13761-2
	RUNX3-AS1	NR_183339.1		n.3838A>G		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX3	ENST00000338888.4	TSL:1	c.53T>C	p.Ile18Thr	missense	Exon 2 of 7	ENSP00000343477.3	Q13761-2
	RUNX3	ENST00000479341.1	TSL:1	n.163T>C		non_coding_transcript_exon	Exon 2 of 3
	RUNX3	ENST00000399916.5	TSL:2	c.53T>C	p.Ile18Thr	missense	Exon 1 of 6	ENSP00000382800.1	Q13761-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Benign	0.96
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.36	T
MetaSVM	Uncertain	0.48	D
PhyloP100		5.8
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.50
Sift	Benign	0.033	D
Sift4G	Benign	0.33	T
Polyphen		1.0	D
Vest4		0.32
MutPred		0.34		Gain of glycosylation at I18 (P = 0.002)
MVP		0.67
MPC		1.6
ClinPred		0.84	D
GERP RS		5.7
PromoterAI		-0.10	Neutral
gMVP		0.22
Mutation Taster		=80/20	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6672420; hg19: chr1-25291010;