rs1060504666

chr21-34799344-G-Cchr21-34799344-G-Achr21-34799344-G-T

Variant summary

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

The NM_001754.5(RUNX1):c.924C>G(p.Ser308Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S308S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RUNX1 NM_001754.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462

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]

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/exons	MANE	UniProt
RUNX1	NM_001754.5	c.924C>G	p.Ser308Arg	missense_variant	8/9	ENST00000675419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX1	ENST00000675419.1	c.924C>G	p.Ser308Arg	missense_variant	8/9		NM_001754.5	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
Cadd	Benign	15
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.52	D;.;.;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.90	D;D;.;D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.59	D;D;D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.7	L;.;.;.
MutationTaster	Benign	0.89	N;N;N;N;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Benign	0.29
Sift	Uncertain	0.0070	D;D;D;D
Sift4G	Benign	0.19	T;T;T;T
Polyphen		0.97	D;D;D;.
Vest4		0.70
MutPred		0.35		Loss of glycosylation at S281 (P = 0.002);.;.;.;
MVP		0.67
MPC		1.5
ClinPred		0.95	D
GERP RS		-2.8
Varity_R		0.32
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr21-36171641;