rs587776517
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP3PP5
The NM_173560.4(RFX6):c.779_780+12del variant causes a splice donor, splice donor 5th base, coding sequence, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
RFX6
NM_173560.4 splice_donor, splice_donor_5th_base, coding_sequence, intron
NM_173560.4 splice_donor, splice_donor_5th_base, coding_sequence, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.52
Genes affected
RFX6 (HGNC:21478): (regulatory factor X6) The nuclear protein encoded by this gene is a member of the regulatory factor X (RFX) family of transcription factors. Studies in mice suggest that this gene is specifically required for the differentiation of islet cells for the production of insulin, but not for the differentiation of pancreatic polypeptide-producing cells. It regulates the transcription factors involved in beta-cell maturation and function, thus, restricting the expression of the beta-cell differentiation and specification genes. Mutations in this gene are associated with Mitchell-Riley syndrome, which is characterized by neonatal diabetes with pancreatic hypoplasia, duodenal and jejunal atresia, and gall bladder agenesis.[provided by RefSeq, Sep 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PVS1
?
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.038392536 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
?
Variant 6-116911037-GACAAGGTATCAATT-G is Pathogenic according to our data. Variant chr6-116911037-GACAAGGTATCAATT-G is described in ClinVar as [Pathogenic]. Clinvar id is 501.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RFX6 | NM_173560.4 | c.779_780+12del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 7/19 | ENST00000332958.3 | ||
RFX6 | XM_011535589.2 | c.673-4967_673-4954del | intron_variant | ||||
RFX6 | XM_017010477.2 | c.401_402+12del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 6/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RFX6 | ENST00000332958.3 | c.779_780+12del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 7/19 | 1 | NM_173560.4 | P1 | ||
RFX6 | ENST00000471966.1 | n.470_471+12del | splice_donor_variant, splice_donor_5th_base_variant, non_coding_transcript_exon_variant, intron_variant | 4/7 | 5 | ||||
RFX6 | ENST00000487683.5 | n.843_844+12del | splice_donor_variant, splice_donor_5th_base_variant, non_coding_transcript_exon_variant, intron_variant | 7/14 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 11, 2010 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at