rs149464542
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_015272.5(RPGRIP1L):āc.1872T>Cā(p.Ser624=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,844 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 (ā ā ).
Frequency
Genomes: š 0.000053 ( 0 hom., cov: 32)
Exomes š: 0.000033 ( 0 hom. )
Consequence
RPGRIP1L
NM_015272.5 synonymous
NM_015272.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.724
Genes affected
RPGRIP1L (HGNC:29168): (RPGRIP1 like) The protein encoded by this gene can localize to the basal body-centrosome complex or to primary cilia and centrosomes in ciliated cells. The encoded protein has been found to interact with nephrocystin-4. Defects in this gene are a cause of Joubert syndrome type 7 (JBTS7) and Meckel syndrome type 5 (MKS5). [provided by RefSeq, Jun 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 16-53652815-A-G is Benign according to our data. Variant chr16-53652815-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 413874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.724 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPGRIP1L | NM_015272.5 | c.1872T>C | p.Ser624= | synonymous_variant | 15/27 | ENST00000647211.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPGRIP1L | ENST00000647211.2 | c.1872T>C | p.Ser624= | synonymous_variant | 15/27 | NM_015272.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152228Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000478 AC: 12AN: 250880Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135570
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GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461616Hom.: 0 Cov.: 32 AF XY: 0.0000358 AC XY: 26AN XY: 727082
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74384
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
RPGRIP1L-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 02, 2023 | 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). - |
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 18, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at