Genetic Variant RUNX1T1:p.Met580Thr (chr8-91960318-A-G) – 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_175634.3(RUNX1T1):c.1739T>C(p.Met580Thr) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

RUNX1T1
NM_175634.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.38

Publications

0 publications found

Variant links:

Genes affected

RUNX1T1 (HGNC:1535): (RUNX1 partner transcriptional co-repressor 1) This gene encodes a member of the myeloid translocation gene family which interact with DNA-bound transcription factors and recruit a range of corepressors to facilitate transcriptional repression. The t(8;21)(q22;q22) translocation is one of the most frequent karyotypic abnormalities in acute myeloid leukemia. The translocation produces a chimeric gene made up of the 5'-region of the runt-related transcription factor 1 gene fused to the 3'-region of this gene. The chimeric protein is thought to associate with the nuclear corepressor/histone deacetylase complex to block hematopoietic differentiation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2010]

RUNX1T1 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, PanelApp Australia

RUNX1T1 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=0.0777463).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175634.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RUNX1T1	NM_175634.3	MANE Select	c.1739T>C	p.Met580Thr	missense	Exon 12 of 12	NP_783552.1	Q06455-1
RUNX1T1	NM_001198679.3		c.1916T>C	p.Met639Thr	missense	Exon 12 of 12	NP_001185608.1	A0A0A0MSU1
RUNX1T1	NM_001395209.1		c.1823T>C	p.Met608Thr	missense	Exon 12 of 12	NP_001382138.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RUNX1T1	ENST00000523629.7	TSL:5 MANE Select	c.1739T>C	p.Met580Thr	missense	Exon 12 of 12	ENSP00000428543.1	Q06455-1
RUNX1T1	ENST00000396218.5	TSL:1	c.1658T>C	p.Met553Thr	missense	Exon 11 of 11	ENSP00000379520.1	Q06455-2
RUNX1T1	ENST00000518844.5	TSL:1	c.1658T>C	p.Met553Thr	missense	Exon 15 of 15	ENSP00000430728.1	Q06455-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.26

Eigen

Benign

-0.14

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.84

M_CAP

Benign

0.0070

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

5.4

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.24

REVEL

Benign

0.064

Sift

Benign

0.33

Sift4G

Benign

0.65

Polyphen

0.0030

Vest4

0.18

MutPred

0.17

Gain of glycosylation at M580 (P = 0.0019)

MVP

0.11

MPC

0.80

ClinPred

0.51

GERP RS

5.9

Varity_R

0.15

gMVP

0.15

Mutation Taster

=84/16

polymorphism

(source)

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

Publications

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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