chr6-116928921-C-T
Variant summary
Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_173560.4(RFX6):c.2561C>T(p.Ser854Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000829 in 1,613,588 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_173560.4 missense
Scores
Clinical Significance
Conservation
Publications
- Martinez-Frias syndromeInheritance: AR Classification: DEFINITIVE Submitted by: G2P
- hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndromeInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
- Mitchell-Riley syndromeInheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
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ACMG classification
Our verdict: Benign. The variant received -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RFX6 | NM_173560.4 | c.2561C>T | p.Ser854Leu | missense_variant | Exon 18 of 19 | ENST00000332958.3 | NP_775831.2 | |
RFX6 | XM_011535589.2 | c.2453C>T | p.Ser818Leu | missense_variant | Exon 17 of 18 | XP_011533891.1 | ||
RFX6 | XM_017010477.2 | c.2183C>T | p.Ser728Leu | missense_variant | Exon 17 of 18 | XP_016865966.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000900 AC: 137AN: 152150Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.000899 AC: 226AN: 251414 AF XY: 0.000868 show subpopulations
GnomAD4 exome AF: 0.000822 AC: 1201AN: 1461320Hom.: 1 Cov.: 32 AF XY: 0.000801 AC XY: 582AN XY: 727024 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000900 AC: 137AN: 152268Hom.: 0 Cov.: 32 AF XY: 0.000980 AC XY: 73AN XY: 74466 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Monogenic diabetes Uncertain:1
ACMG Criteria:PP3, BP4 -
Hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome Uncertain:1
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RFX6-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at