chr1-24964519-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001031680.2(RUNX3):​c.53T>G​(p.Ile18Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,457,388 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RUNX3 NM_001031680.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.82

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39227727).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNX3	NM_001031680.2	c.53T>G	p.Ile18Ser	missense_variant	Exon 1 of 6		NP_001026850.1
RUNX3	NM_001320672.1	c.53T>G	p.Ile18Ser	missense_variant	Exon 2 of 7		NP_001307601.1
RUNX3	XM_005246024.5	c.53T>G	p.Ile18Ser	missense_variant	Exon 2 of 7		XP_005246081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNX3	ENST00000338888.4	c.53T>G	p.Ile18Ser	missense_variant	Exon 2 of 7	1		ENSP00000343477.3
RUNX3	ENST00000479341.1	n.163T>G		non_coding_transcript_exon_variant	Exon 2 of 3	1
RUNX3	ENST00000399916.5	c.53T>G	p.Ile18Ser	missense_variant	Exon 1 of 6	2		ENSP00000382800.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457388 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 724602

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	22
DANN	Uncertain	0.99
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.65	T;.
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Uncertain	0.49	D
PROVEAN	Benign	-1.4	N;N
REVEL	Uncertain	0.46
Sift	Uncertain	0.015	D;D
Sift4G	Benign	0.41	T;T
Polyphen		1.0	D;D
Vest4		0.41
MutPred		0.34		Gain of glycosylation at I18 (P = 0.0076);Gain of glycosylation at I18 (P = 0.0076);
MVP		0.69
MPC		1.8
ClinPred		0.96	D
GERP RS		5.7
gMVP		0.42

Splicing

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: chr1-25291010;