rs104894054
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000474.4(TWIST1):c.309C>T(p.Tyr103Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000028 in 1,430,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
TWIST1
NM_000474.4 synonymous
NM_000474.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.83
Genes affected
TWIST1 (HGNC:12428): (twist family bHLH transcription factor 1) This gene encodes a basic helix-loop-helix (bHLH) transcription factor that plays an important role in embryonic development. The encoded protein forms both homodimers and heterodimers that bind to DNA E box sequences and regulate the transcription of genes involved in cranial suture closure during skull development. This protein may also regulate neural tube closure, limb development and brown fat metabolism. This gene is hypermethylated and overexpressed in multiple human cancers, and the encoded protein promotes tumor cell invasion and metastasis, as well as metastatic recurrence. Mutations in this gene cause Saethre-Chotzen syndrome in human patients, which is characterized by craniosynostosis, ptosis and hypertelorism. [provided by RefSeq, Jul 2020]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 7-19117013-G-A is Benign according to our data. Variant chr7-19117013-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2935429.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.83 with no splicing effect.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| TWIST1 | ENST00000242261.6 | c.309C>T | p.Tyr103Tyr | synonymous_variant | Exon 1 of 2 | 1 | NM_000474.4 | ENSP00000242261.5 | ||
| TWIST1 | ENST00000354571.5 | n.105C>T | non_coding_transcript_exon_variant | Exon 1 of 3 | 2 | ENSP00000346582.5 | ||||
| TWIST1 | ENST00000443687.5 | n.-91C>T | upstream_gene_variant | 4 | ENSP00000416986.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000280 AC: 4AN: 1430512Hom.: 0 Cov.: 32 AF XY: 0.00000281 AC XY: 2AN XY: 711210
GnomAD4 exome
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4
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1430512
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32
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2
AN XY:
711210
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GnomAD4 genome
GnomAD4 genome
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32
Bravo
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Saethre-Chotzen syndrome;C4551902:TWIST1-related craniosynostosis Benign:1
Jan 29, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Name
Calibrated prediction
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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