chr2-44942146-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_005413.4(SIX3):c.42C>T(p.Phe14=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000108 in 1,598,266 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 0.000072 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
SIX3
NM_005413.4 synonymous
NM_005413.4 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 3.91
Genes affected
SIX3 (HGNC:10889): (SIX homeobox 3) This gene encodes a member of the sine oculis homeobox transcription factor family. The encoded protein plays a role in eye development. Mutations in this gene have been associated with holoprosencephaly type 2. [provided by RefSeq, Oct 2009]
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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=-0.41).
BP6
?
Variant 2-44942146-C-T is Benign according to our data. Variant chr2-44942146-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 772996.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-44942146-C-T is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0000724 (11/151980) while in subpopulation NFE AF= 0.000162 (11/67926). AF 95% confidence interval is 0.0000906. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIX3 | NM_005413.4 | c.42C>T | p.Phe14= | synonymous_variant | 1/2 | ENST00000260653.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIX3 | ENST00000260653.5 | c.42C>T | p.Phe14= | synonymous_variant | 1/2 | 1 | NM_005413.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000724 AC: 11AN: 151980Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000512 AC: 12AN: 234556Hom.: 0 AF XY: 0.0000623 AC XY: 8AN XY: 128428
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GnomAD4 exome AF: 0.000112 AC: 162AN: 1446286Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 77AN XY: 719902
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 19, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at