19-45765633-C-T
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The NM_175875.5(SIX5):c.2088G>A(p.Leu696=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,612,572 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 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
SIX5
NM_175875.5 synonymous
NM_175875.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.00200
Genes affected
SIX5 (HGNC:10891): (SIX homeobox 5) The protein encoded by this gene is a homeodomain-containing transcription factor that appears to function in the regulation of organogenesis. This gene is located downstream of the dystrophia myotonica-protein kinase gene. Mutations in this gene are a cause of branchiootorenal syndrome type 2. [provided by RefSeq, Jul 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant 19-45765633-C-T is Benign according to our data. Variant chr19-45765633-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2992499.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45765633-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=0.002 with no splicing effect.
BS2
High AC in GnomAd4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SIX5 | NM_175875.5 | c.2088G>A | p.Leu696= | synonymous_variant | 3/3 | ENST00000317578.7 | NP_787071.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SIX5 | ENST00000317578.7 | c.2088G>A | p.Leu696= | synonymous_variant | 3/3 | 1 | NM_175875.5 | ENSP00000316842 | P1 | |
ENST00000559756.1 | n.849C>T | non_coding_transcript_exon_variant | 1/2 | 3 | ||||||
SIX5 | ENST00000560160.1 | c.*298G>A | 3_prime_UTR_variant | 2/2 | 2 | ENSP00000453239 | ||||
SIX5 | ENST00000560168.1 | c.*1514G>A | 3_prime_UTR_variant | 3/3 | 4 | ENSP00000453189 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152204Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000200 AC: 5AN: 250338Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135570
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1460368Hom.: 0 Cov.: 29 AF XY: 0.0000110 AC XY: 8AN XY: 726512
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74346
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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 | Labcorp Genetics (formerly Invitae), Labcorp | May 17, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
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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