X-37659605-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001170331.2(LANCL3):c.841G>A(p.Gly281Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000935 in 1,208,116 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 28 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00053 ( 0 hom., 14 hem., cov: 22)
Exomes 𝑓: 0.000050 ( 0 hom. 14 hem. )
Consequence
LANCL3
NM_001170331.2 missense
NM_001170331.2 missense
Scores
2
3
12
Clinical Significance
Conservation
PhyloP100: 8.55
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.10089305).
BS2
High Hemizygotes in GnomAd4 at 14 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LANCL3 | NM_001170331.2 | c.841G>A | p.Gly281Ser | missense_variant | 3/5 | ENST00000378619.4 | |
LANCL3 | NM_198511.3 | c.841G>A | p.Gly281Ser | missense_variant | 3/6 | ||
LANCL3 | XM_011543904.3 | c.295G>A | p.Gly99Ser | missense_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LANCL3 | ENST00000378619.4 | c.841G>A | p.Gly281Ser | missense_variant | 3/5 | 1 | NM_001170331.2 | P1 | |
LANCL3 | ENST00000378621.7 | c.841G>A | p.Gly281Ser | missense_variant | 3/6 | 1 | |||
LANCL3 | ENST00000614025.4 | c.841G>A | p.Gly281Ser | missense_variant | 3/5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000526 AC: 58AN: 110248Hom.: 0 Cov.: 22 AF XY: 0.000430 AC XY: 14AN XY: 32550
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GnomAD3 exomes AF: 0.000131 AC: 24AN: 182681Hom.: 0 AF XY: 0.0000446 AC XY: 3AN XY: 67307
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GnomAD4 exome AF: 0.0000501 AC: 55AN: 1097814Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 14AN XY: 363216
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GnomAD4 genome AF: 0.000526 AC: 58AN: 110302Hom.: 0 Cov.: 22 AF XY: 0.000429 AC XY: 14AN XY: 32614
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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 | Nov 22, 2021 | The c.841G>A (p.G281S) alteration is located in exon 3 (coding exon 3) of the LANCL3 gene. This alteration results from a G to A substitution at nucleotide position 841, causing the glycine (G) at amino acid position 281 to be replaced by a serine (S). 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;.;T
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N;N
REVEL
Benign
Sift
Benign
.;T;T
Sift4G
Benign
T;T;T
Polyphen
P;P;P
Vest4
MVP
MPC
0.99
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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