7-105548580-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_021930.6(RINT1):āc.866A>Gā(p.Gln289Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q289P) has been classified as Uncertain significance.
Frequency
Consequence
NM_021930.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RINT1 | NM_021930.6 | c.866A>G | p.Gln289Arg | missense_variant | 7/15 | ENST00000257700.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RINT1 | ENST00000257700.7 | c.866A>G | p.Gln289Arg | missense_variant | 7/15 | 1 | NM_021930.6 | P1 | |
RINT1 | ENST00000497979.5 | c.*471A>G | 3_prime_UTR_variant, NMD_transcript_variant | 7/15 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251456Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135898
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461860Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727232
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 07, 2019 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RINT1-related disease. ClinVar contains an entry for this variant (Variation ID:Ā¬ā 410795). This variant is present in population databases (rs747465384, ExAC 0.001%). This sequence change replaces glutamine with arginine at codon 289 of the RINT1 protein (p.Gln289Arg). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and arginine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at