rs1397164331

Positions:

• chr21-34792524-C-A
• chr21-34792524-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001754.5(RUNX1):​c.1054G>T​(p.Ala352Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RUNX1 NM_001754.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26278853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUNX1	NM_001754.5	c.1054G>T	p.Ala352Ser	missense_variant	9/9	ENST00000675419.1	NP_001745.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000675419.1	c.1054G>T	p.Ala352Ser	missense_variant	9/9		NM_001754.5	ENSP00000501943	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Uncertain	0.65	D;.;.;.
Eigen	Benign	0.041
Eigen_PC	Benign	0.089
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.93	D;D;.;D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	2.0	M;.;.;.
MutationTaster	Benign	0.69	D;D;D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.014	D;D;D;T
Sift4G	Benign	0.35	T;T;T;T
Polyphen		0.10	B;P;P;.
Vest4		0.32
MutPred		0.24		Gain of glycosylation at A325 (P = 0.0054);.;.;.;
MVP		0.65
MPC		1.1
ClinPred		0.79	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.44

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

LitVar

Other links and lift over

dbSNP: rs1397164331; hg19: chr21-36164821;