Genetic Variant NM_001754.5:c.787C>G (chr21-34834428-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001754.5(RUNX1):c.787C>G(p.Pro263Ala) 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. P263S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Consequence

RUNX1
NM_001754.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.61

Publications

0 publications found

Variant links:

Genes affected

RUNX1 (HGNC:10471): (RUNX family transcription factor 1) Core binding factor (CBF) is a heterodimeric transcription factor that binds to the core element of many enhancers and promoters. The protein encoded by this gene represents the alpha subunit of CBF and is thought to be involved in the development of normal hematopoiesis. Chromosomal translocations involving this gene are well-documented and have been associated with several types of leukemia. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RUNX1 Gene-Disease associations (from GenCC):

hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
acute myeloid leukemia
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

RUNX1 links:

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ACMG classification

Classification was made for transcript

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=0.18697965).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001754.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RUNX1	NM_001754.5	MANE Select	c.787C>G	p.Pro263Ala	missense	Exon 7 of 9	NP_001745.2
RUNX1	NM_001001890.3		c.706C>G	p.Pro236Ala	missense	Exon 4 of 6	NP_001001890.1
RUNX1	NM_001122607.2		c.706C>G	p.Pro236Ala	missense	Exon 4 of 5	NP_001116079.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RUNX1	ENST00000675419.1	MANE Select	c.787C>G	p.Pro263Ala	missense	Exon 7 of 9	ENSP00000501943.1
RUNX1	ENST00000300305.7	TSL:1	c.787C>G	p.Pro263Ala	missense	Exon 6 of 8	ENSP00000300305.3
RUNX1	ENST00000344691.8	TSL:1	c.706C>G	p.Pro236Ala	missense	Exon 4 of 6	ENSP00000340690.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.46

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.19

MetaSVM

Pathogenic

0.89

MutationAssessor

Benign

0.92

PhyloP100

4.6

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.81

REVEL

Benign

0.28

Sift

Benign

0.96

Sift4G

Benign

0.73

Polyphen

0.42

Vest4

0.45

MutPred

0.16

Loss of glycosylation at P236 (P = 0.08)

MVP

0.95

MPC

0.60

ClinPred

0.34

GERP RS

4.2

Varity_R

0.071

gMVP

0.29

Mutation Taster

=60/40

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over