chr1-70148603-C-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000370952.4(LRRC40):āc.1587G>Cā(p.Gln529His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,964 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000027 ( 0 hom. )
Consequence
LRRC40
ENST00000370952.4 missense
ENST00000370952.4 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 1.86
Genes affected
LRRC40 (HGNC:26004): (leucine rich repeat containing 40) Predicted to enable protein serine/threonine phosphatase activity. Predicted to be involved in signal transduction. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRRC40 | NM_017768.5 | c.1587G>C | p.Gln529His | missense_variant | 14/15 | ENST00000370952.4 | NP_060238.3 | |
LRRC40 | XM_011541763.2 | c.933G>C | p.Gln311His | missense_variant | 12/13 | XP_011540065.1 | ||
LRRC40 | XM_047424520.1 | c.933G>C | p.Gln311His | missense_variant | 12/13 | XP_047280476.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LRRC40 | ENST00000370952.4 | c.1587G>C | p.Gln529His | missense_variant | 14/15 | 1 | NM_017768.5 | ENSP00000359990 | P1 | |
LRRC7 | ENST00000441830.1 | n.192+598C>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460964Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726842
GnomAD4 exome
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4
AN:
1460964
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Cov.:
30
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2
AN XY:
726842
Gnomad4 AFR exome
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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
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 15, 2023 | The c.1587G>C (p.Q529H) alteration is located in exon 14 (coding exon 14) of the LRRC40 gene. This alteration results from a G to C substitution at nucleotide position 1587, causing the glutamine (Q) at amino acid position 529 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Loss of stability (P = 0.1052);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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
Publications
No publications associated with this variant yet.