rs947627767

Variant names:

• chr1-24902486-G-A
• rs947627767
• NM_004350.3:c.884C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-24902486-G-A
• chr1-24902486-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004350.3(RUNX3):​c.884C>T​(p.Ala295Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,600,308 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: 0.0000021 (0 hom.)
• Consequence: RUNX3 NM_004350.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.01
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21052286).

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.884C>T	p.Ala295Val	missense	Exon 5 of 5	NP_004341.1	Q13761-1
	RUNX3	NM_001031680.2		c.926C>T	p.Ala309Val	missense	Exon 6 of 6	NP_001026850.1	Q13761-2
	RUNX3	NM_001320672.1		c.926C>T	p.Ala309Val	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.884C>T	p.Ala295Val	missense	Exon 5 of 5	ENSP00000308051.6	Q13761-1
	RUNX3	ENST00000338888.4	TSL:1	c.926C>T	p.Ala309Val	missense	Exon 7 of 7	ENSP00000343477.3	Q13761-2
	RUNX3	ENST00000399916.5	TSL:2	c.926C>T	p.Ala309Val	missense	Exon 6 of 6	ENSP00000382800.1	Q13761-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152152 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: 0.00000408 AC: 1 AN: 244838 AF XY: 0.00

Gnomad AFR exome AF: 0.0000652

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1448156 Hom.: 0 Cov.: 31 AF XY: 0.00000279 AC XY: 2 AN XY: 717764

African (AFR) AF: 0.0000301 AC: 1 AN: 33250

American (AMR) AF: 0.00 AC: 0 AN: 44342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25734

East Asian (EAS) AF: 0.00 AC: 0 AN: 39336

South Asian (SAS) AF: 0.00 AC: 0 AN: 85782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1102198

Other (OTH) AF: 0.00 AC: 0 AN: 59656

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74336

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.13
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Benign	-0.065
Eigen_PC	Benign	-0.0051
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	0.62	D
MutationAssessor	Benign	1.3	L
PhyloP100		2.0
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.91	N
REVEL	Uncertain	0.34
Sift	Benign	0.073	T
Sift4G	Benign	0.19	T
Polyphen		0.57	P
Vest4		0.092
MutPred		0.36		Loss of glycosylation at S290 (P = 0.0982)
MVP		0.68
MPC		0.76
ClinPred		0.14	T
GERP RS		3.2
Varity_R		0.078
gMVP		0.14
Mutation Taster		=81/19	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: rs947627767; hg19: chr1-25228977; COSMIC: COSV100136741; COSMIC: COSV100136741;