chr1-100159405-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_144620.4(LRRC39):c.230C>T(p.Ser77Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00023 in 1,606,130 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 0 hom. )
Consequence
LRRC39
NM_144620.4 missense
NM_144620.4 missense
Scores
2
4
8
Clinical Significance
Conservation
PhyloP100: 4.28
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 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.25868577).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRC39 | NM_144620.4 | c.230C>T | p.Ser77Phe | missense_variant | 5/10 | ENST00000370137.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRC39 | ENST00000370137.6 | c.230C>T | p.Ser77Phe | missense_variant | 5/10 | 1 | NM_144620.4 | P1 | |
LRRC39 | ENST00000370138.1 | c.230C>T | p.Ser77Phe | missense_variant | 5/11 | 5 | |||
LRRC39 | ENST00000342895.8 | c.230C>T | p.Ser77Phe | missense_variant | 5/10 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000256 AC: 39AN: 152150Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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152150
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32
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GnomAD3 exomes AF: 0.000262 AC: 64AN: 244616Hom.: 0 AF XY: 0.000264 AC XY: 35AN XY: 132410
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GnomAD4 exome AF: 0.000227 AC: 330AN: 1453862Hom.: 0 Cov.: 30 AF XY: 0.000235 AC XY: 170AN XY: 723090
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GnomAD4 genome ? AF: 0.000256 AC: 39AN: 152268Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74450
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ExAC
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28
Asia WGS
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3478
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 | Sep 16, 2021 | The c.230C>T (p.S77F) alteration is located in exon 5 (coding exon 3) of the LRRC39 gene. This alteration results from a C to T substitution at nucleotide position 230, causing the serine (S) at amino acid position 77 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
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
0.25
ClinPred
T
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