chr17-76733148-T-G
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_001080510.5(METTL23):āc.255T>Gā(p.Ser85=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,613,934 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 (ā ā ).
Frequency
Genomes: š 0.00083 ( 0 hom., cov: 33)
Exomes š: 0.000086 ( 0 hom. )
Consequence
METTL23
NM_001080510.5 synonymous
NM_001080510.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.71
Genes affected
METTL23 (HGNC:26988): (methyltransferase 23, arginine) The protein encoded by this gene functions as a transcription factor regulator in the transcriptional pathway for human cognition. It is a partner of the alpha subunit of the GA-binding protein transcription factor. Mutations in this gene cause mild autosomal recessive intellectual disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 17-76733148-T-G is Benign according to our data. Variant chr17-76733148-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 737135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.71 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000827 (126/152332) while in subpopulation AFR AF= 0.00267 (111/41584). AF 95% confidence interval is 0.00227. There are 0 homozygotes in gnomad4. There are 64 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
METTL23 | NM_001080510.5 | c.255T>G | p.Ser85= | synonymous_variant | 3/5 | ENST00000341249.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
METTL23 | ENST00000341249.11 | c.255T>G | p.Ser85= | synonymous_variant | 3/5 | 1 | NM_001080510.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000828 AC: 126AN: 152214Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000173 AC: 43AN: 249000Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 135082
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GnomAD4 exome AF: 0.0000855 AC: 125AN: 1461602Hom.: 0 Cov.: 33 AF XY: 0.0000701 AC XY: 51AN XY: 727060
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GnomAD4 genome AF: 0.000827 AC: 126AN: 152332Hom.: 0 Cov.: 33 AF XY: 0.000859 AC XY: 64AN XY: 74494
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 14, 2019 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at