rs1317404916

Variant names:

• chr1-24902196-C-T
• rs1317404916
• NM_004350.3:c.1174G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-24902196-C-T
• chr1-24902196-C-A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_004350.3(RUNX3):​c.1174G>A​(p.Gly392Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000115 in 1,569,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: RUNX3 NM_004350.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.73
• Publications: 0 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]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.33753252).
• BS2: High AC in GnomAdExome4 at 17 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004350.3. 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_004350.3	MANE Select	c.1174G>A	p.Gly392Ser	missense	Exon 5 of 5	NP_004341.1	Q13761-1
	RUNX3	NM_001031680.2		c.1216G>A	p.Gly406Ser	missense	Exon 6 of 6	NP_001026850.1	Q13761-2
	RUNX3	NM_001320672.1		c.1216G>A	p.Gly406Ser	missense	Exon 7 of 7	NP_001307601.1	Q13761-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX3	ENST00000308873.11	TSL:1 MANE Select	c.1174G>A	p.Gly392Ser	missense	Exon 5 of 5	ENSP00000308051.6	Q13761-1
	RUNX3	ENST00000338888.4	TSL:1	c.1216G>A	p.Gly406Ser	missense	Exon 7 of 7	ENSP00000343477.3	Q13761-2
	RUNX3	ENST00000399916.5	TSL:2	c.1216G>A	p.Gly406Ser	missense	Exon 6 of 6	ENSP00000382800.1	Q13761-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152240 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000572 AC: 1 AN: 174700 AF XY: 0.0000106

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000138

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000120 AC: 17 AN: 1416950 Hom.: 0 Cov.: 31 AF XY: 0.0000157 AC XY: 11 AN XY: 700692

African (AFR) AF: 0.00 AC: 0 AN: 32904

American (AMR) AF: 0.0000528 AC: 2 AN: 37872

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25308

East Asian (EAS) AF: 0.00 AC: 0 AN: 37996

South Asian (SAS) AF: 0.00 AC: 0 AN: 80950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4366

European-Non Finnish (NFE) AF: 0.0000119 AC: 13 AN: 1091184

Other (OTH) AF: 0.0000341 AC: 2 AN: 58632

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152240 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74380

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000902 Hom.: 0

Bravo AF: 0.0000189

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	0.15
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.2	L
PhyloP100		5.7
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.23
Sift	Benign	0.058	T
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.40
MVP		0.47
MPC		1.8
ClinPred		0.97	D
GERP RS		4.2
Varity_R		0.56
gMVP		0.59
Mutation Taster		=68/32	polymorphism

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: rs1317404916; hg19: chr1-25228687; COSMIC: COSV58245537;