chr7-19116722-C-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7
The NM_000474.4(TWIST1):c.600G>C(p.Ala200=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000933 in 1,607,684 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: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
TWIST1
NM_000474.4 synonymous
NM_000474.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.111
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.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
Variant 7-19116722-C-G is Benign according to our data. Variant chr7-19116722-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2923233.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.111 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TWIST1 | NM_000474.4 | c.600G>C | p.Ala200= | synonymous_variant | 1/2 | ENST00000242261.6 | |
TWIST1 | NR_149001.2 | n.915G>C | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TWIST1 | ENST00000242261.6 | c.600G>C | p.Ala200= | synonymous_variant | 1/2 | 1 | NM_000474.4 | P1 | |
TWIST1 | ENST00000354571.5 | c.399G>C | p.Ala133= | synonymous_variant, NMD_transcript_variant | 1/3 | 2 | |||
TWIST1 | ENST00000443687.5 | c.204G>C | p.Ala68= | synonymous_variant, NMD_transcript_variant | 1/4 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000847 AC: 2AN: 236118Hom.: 0 AF XY: 0.00000780 AC XY: 1AN XY: 128190
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GnomAD4 exome AF: 0.00000893 AC: 13AN: 1455502Hom.: 0 Cov.: 32 AF XY: 0.00000691 AC XY: 5AN XY: 723476
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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
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 06, 2023 | - - |
Computational scores
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Benign
Cadd
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Dann
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at