rs753201950

Variant names:

• chr1-24902585-C-A
• NM_004350.3:c.785G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-24902585-C-A
• chr1-24902585-C-T

Variant summary

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

The NM_004350.3(RUNX3):​c.785G>T​(p.Arg262Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000709 in 1,410,256 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R262H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RUNX3 NM_004350.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.71

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNX3	NM_004350.3	c.785G>T	p.Arg262Leu	missense_variant	Exon 5 of 5	ENST00000308873.11	NP_004341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNX3	ENST00000308873.11	c.785G>T	p.Arg262Leu	missense_variant	Exon 5 of 5	1	NM_004350.3	ENSP00000308051.6
RUNX3	ENST00000338888.4	c.827G>T	p.Arg276Leu	missense_variant	Exon 7 of 7	1		ENSP00000343477.3
RUNX3	ENST00000399916.5	c.827G>T	p.Arg276Leu	missense_variant	Exon 6 of 6	2		ENSP00000382800.1
RUNX3	ENST00000496967.1	n.559G>T		non_coding_transcript_exon_variant	Exon 5 of 5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1410256 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 693842

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.25e-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
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.83	.;D;.
Eigen	Benign	0.077
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D;D;.
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Uncertain	-0.052	T
MutationAssessor	Uncertain	2.5	.;M;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-4.6	D;D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.047	D;T;D
Polyphen		0.99	.;D;.
Vest4		0.56
MutPred		0.17		.;Gain of helix (P = 0.005);.;
MVP		0.69
MPC		0.93
ClinPred		0.99	D
GERP RS		3.3
Varity_R		0.66
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-25229076;