6-45338734-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_001024630.4(RUNX2):c.58+9950C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,016 control chromosomes in the GnomAD database, including 2,034 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.15 ( 2034 hom., cov: 32)
Consequence
RUNX2
NM_001024630.4 intron
NM_001024630.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.09
Genes affected
RUNX2 (HGNC:10472): (RUNX family transcription factor 2) This gene is a member of the RUNX family of transcription factors and encodes a nuclear protein with an Runt DNA-binding domain. This protein is essential for osteoblastic differentiation and skeletal morphogenesis and acts as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. The protein can bind DNA both as a monomer or, with more affinity, as a subunit of a heterodimeric complex. Two regions of potential trinucleotide repeat expansions are present in the N-terminal region of the encoded protein, and these and other mutations in this gene have been associated with the bone development disorder cleidocranial dysplasia (CCD). Transcript variants that encode different protein isoforms result from the use of alternate promoters as well as alternate splicing. [provided by RefSeq, Jul 2016]
SUPT3H (HGNC:11466): (SPT3 homolog, SAGA and STAGA complex component) Enables transcription coactivator activity. Involved in histone H3 acetylation and histone deubiquitination. Located in nucleoplasm. Part of SAGA complex and transcription factor TFTC complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RUNX2 | NM_001024630.4 | c.58+9950C>T | intron_variant | ENST00000647337.2 | |||
SUPT3H | NM_003599.4 | c.101+26467G>A | intron_variant | ENST00000371459.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUPT3H | ENST00000371459.6 | c.101+26467G>A | intron_variant | 1 | NM_003599.4 | P1 | |||
RUNX2 | ENST00000647337.2 | c.58+9950C>T | intron_variant | NM_001024630.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.154 AC: 23329AN: 151896Hom.: 2033 Cov.: 32
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GnomAD4 genome ? AF: 0.154 AC: 23344AN: 152016Hom.: 2034 Cov.: 32 AF XY: 0.159 AC XY: 11787AN XY: 74316
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834
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3474
ClinVar
Not reported inComputational scores
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Name
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Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at