chr2-44941782-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.-323C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00519 in 332,676 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0049 ( 4 hom., cov: 30)
Exomes 𝑓: 0.0054 ( 7 hom. )
Consequence
SIX3
NM_005413.4 5_prime_UTR
NM_005413.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.44
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=-0.32).
BP6
?
Variant 2-44941782-C-T is Benign according to our data. Variant chr2-44941782-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1197315.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00488 (742/152084) while in subpopulation AMR AF= 0.00798 (122/15288). AF 95% confidence interval is 0.00683. There are 4 homozygotes in gnomad4. There are 346 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
?
High AC in GnomAd at 742 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIX3 | NM_005413.4 | c.-323C>T | 5_prime_UTR_variant | 1/2 | ENST00000260653.5 | ||
SIX3-AS1 | NR_103786.1 | n.97G>A | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIX3 | ENST00000260653.5 | c.-323C>T | 5_prime_UTR_variant | 1/2 | 1 | NM_005413.4 | P1 | ||
SIX3-AS1 | ENST00000419364.3 | n.135G>A | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00488 AC: 742AN: 151966Hom.: 4 Cov.: 30
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GnomAD4 exome AF: 0.00544 AC: 983AN: 180592Hom.: 7 Cov.: 0 AF XY: 0.00503 AC XY: 478AN XY: 95106
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GnomAD4 genome ? AF: 0.00488 AC: 742AN: 152084Hom.: 4 Cov.: 30 AF XY: 0.00465 AC XY: 346AN XY: 74348
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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 | GeneDx | Sep 16, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at