chr14-60648862-G-C
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_Strong
The NM_005982.4(SIX1):c.328C>G(p.Arg110Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R110Q) has been classified as Pathogenic.
Frequency
Consequence
NM_005982.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIX1 | NM_005982.4 | c.328C>G | p.Arg110Gly | missense_variant | 1/2 | ENST00000645694.3 | |
SIX1 | XM_017021602.3 | c.328C>G | p.Arg110Gly | missense_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIX1 | ENST00000645694.3 | c.328C>G | p.Arg110Gly | missense_variant | 1/2 | NM_005982.4 | P1 | ||
SIX1 | ENST00000554986.2 | c.42-2285C>G | intron_variant | 3 | |||||
SIX1 | ENST00000553535.2 | n.249-2285C>G | intron_variant, non_coding_transcript_variant | 3 | |||||
SIX1 | ENST00000555955.3 | n.1198-2285C>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Branchiootic syndrome 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Feb 23, 2021 | The inherited c.328C>G, p.Arg110Gly missense variant identified in the SIX1 gene has been reported in the literature in a patient with Brachio-oto-renal syndrome [PMID: 24901346]. This variant is absent in the gnomAD v3.1database, indicating this is a rare allele. In silico analysis predicts deleterious effect [PMID:27268795]and the position is strongly conserved (GERP++ = 5.64). Based on the available evidence, the missense variant c.328C>G, p.Arg110Gly in the SIX1 gene is classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.