rs1135401780
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001370785.2(LRRC7):c.3630T>G(p.Tyr1210Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. 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 (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
LRRC7
NM_001370785.2 stop_gained
NM_001370785.2 stop_gained
Scores
2
2
3
Clinical Significance
Conservation
PhyloP100: 0.192
Genes affected
LRRC7 (HGNC:18531): (leucine rich repeat containing 7) Predicted to be involved in several processes, including establishment or maintenance of epithelial cell apical/basal polarity; positive regulation of neuron projection development; and receptor clustering. Located in several cellular components, including centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRC7 | NM_001370785.2 | c.3630T>G | p.Tyr1210Ter | stop_gained | 21/27 | ENST00000651989.2 | |
LRRC7-AS1 | XR_001738107.2 | n.163-490A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRC7 | ENST00000651989.2 | c.3630T>G | p.Tyr1210Ter | stop_gained | 21/27 | NM_001370785.2 | P1 | ||
LRRC7 | ENST00000415775.2 | c.1368T>G | p.Tyr456Ter | stop_gained | 15/21 | 1 | |||
LRRC7 | ENST00000310961.9 | c.3531T>G | p.Tyr1177Ter | stop_gained | 22/27 | 5 | |||
LRRC7 | ENST00000651217.1 | n.3546T>G | non_coding_transcript_exon_variant | 19/25 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Intellectual disability Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg | Aug 01, 2017 | De novo LOF variant identified in a male patient with IQ 70, absence epilepsy during first years, obesity, muscle and joint pain, migraine. LRRC7 encodes a brain-specific scaffold protein in postsynaptic densities and contains a PDZ domain. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at