12-49104449-T-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_018113.4(LMBR1L):āc.434A>Gā(p.Lys145Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000207 in 1,451,974 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
LMBR1L
NM_018113.4 missense, splice_region
NM_018113.4 missense, splice_region
Scores
1
7
11
Splicing: ADA: 0.6810
2
Clinical Significance
Conservation
PhyloP100: 5.08
Genes affected
LMBR1L (HGNC:18268): (limb development membrane protein 1 like) Enables transmembrane signaling receptor activity. Involved in receptor-mediated endocytosis and signal transduction. Located in endoplasmic reticulum membrane and plasma membrane. Is integral component of plasma membrane. [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 | UniProt |
---|---|---|---|---|---|---|---|
LMBR1L | NM_018113.4 | c.434A>G | p.Lys145Arg | missense_variant, splice_region_variant | 5/17 | ENST00000267102.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LMBR1L | ENST00000267102.13 | c.434A>G | p.Lys145Arg | missense_variant, splice_region_variant | 5/17 | 1 | NM_018113.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000207 AC: 3AN: 1451974Hom.: 0 Cov.: 29 AF XY: 0.00000277 AC XY: 2AN XY: 723146
GnomAD4 exome
AF:
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3
AN:
1451974
Hom.:
Cov.:
29
AF XY:
AC XY:
2
AN XY:
723146
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 | Apr 13, 2022 | The c.434A>G (p.K145R) alteration is located in exon 5 (coding exon 5) of the LMBR1L gene. This alteration results from a A to G substitution at nucleotide position 434, causing the lysine (K) at amino acid position 145 to be replaced by an arginine (R). 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;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Gain of catalytic residue at A141 (P = 0);Gain of catalytic residue at A141 (P = 0);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
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.