1-100160485-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_144620.4(LRRC39):c.200T>C(p.Ile67Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,612,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00022 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
LRRC39
NM_144620.4 missense
NM_144620.4 missense
Scores
2
7
5
Clinical Significance
Conservation
PhyloP100: 8.45
Genes affected
LRRC39 (HGNC:28228): (leucine rich repeat containing 39) Predicted to enable protein serine/threonine phosphatase activity. Predicted to be involved in signal transduction. Predicted to be located in M band. Predicted to be active in cytoplasm and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.806
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRC39 | NM_144620.4 | c.200T>C | p.Ile67Thr | missense_variant | 4/10 | ENST00000370137.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRC39 | ENST00000370137.6 | c.200T>C | p.Ile67Thr | missense_variant | 4/10 | 1 | NM_144620.4 | P1 | |
LRRC39 | ENST00000370138.1 | c.200T>C | p.Ile67Thr | missense_variant | 4/11 | 5 | |||
LRRC39 | ENST00000342895.8 | c.200T>C | p.Ile67Thr | missense_variant | 4/10 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000217 AC: 33AN: 152142Hom.: 0 Cov.: 31
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250498Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135432
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GnomAD4 exome AF: 0.0000253 AC: 37AN: 1460708Hom.: 0 Cov.: 30 AF XY: 0.0000275 AC XY: 20AN XY: 726702
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GnomAD4 genome ? AF: 0.000217 AC: 33AN: 152142Hom.: 0 Cov.: 31 AF XY: 0.000269 AC XY: 20AN XY: 74330
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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 | Dec 08, 2023 | The c.200T>C (p.I67T) alteration is located in exon 4 (coding exon 2) of the LRRC39 gene. This alteration results from a T to C substitution at nucleotide position 200, causing the isoleucine (I) at amino acid position 67 to be replaced by a threonine (T). 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
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;D;D
Vest4
MVP
MPC
0.32
ClinPred
D
GERP RS
Varity_R
gMVP
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