NM_006816.3:c.813G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006816.3(LMAN2):​c.813G>T​(p.Met271Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LMAN2
NM_006816.3 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.28
Variant links:
Genes affected
LMAN2 (HGNC:16986): (lectin, mannose binding 2) This gene encodes a type I transmembrane lectin that shuttles between the endoplasmic reticulum, the Golgi apparatus and the plasma membrane. The encoded protein binds high mannose type glycoproteins and may facilitate their sorting, trafficking and quality control. [provided by RefSeq, Oct 2008]

Genome browser will be placed here

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 rank MANE Protein UniProt
LMAN2NM_006816.3 linkc.813G>T p.Met271Ile missense_variant Exon 7 of 8 ENST00000303127.12 NP_006807.1 Q12907A0A384NPY7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LMAN2ENST00000303127.12 linkc.813G>T p.Met271Ile missense_variant Exon 7 of 8 1 NM_006816.3 ENSP00000303366.7 Q12907

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000798
AC:
2
AN:
250730
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135670
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000579
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461140
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726872
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 30, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.813G>T (p.M271I) alteration is located in exon 7 (coding exon 7) of the LMAN2 gene. This alteration results from a G to T substitution at nucleotide position 813, causing the methionine (M) at amino acid position 271 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
23
DANN
Benign
0.97
DEOGEN2
Benign
0.064
T;.;.
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.073
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.84
T;T;T
M_CAP
Benign
0.0097
T
MetaRNN
Benign
0.21
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L;.;.
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-0.95
N;N;N
REVEL
Benign
0.070
Sift
Benign
0.76
T;T;T
Sift4G
Benign
0.81
T;T;T
Polyphen
0.0
B;B;.
Vest4
0.32
MutPred
0.48
Gain of methylation at K272 (P = 0.0444);Gain of methylation at K272 (P = 0.0444);.;
MVP
0.55
MPC
0.38
ClinPred
0.20
T
GERP RS
3.6
Varity_R
0.12
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.26
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.26
Position offset: -4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1266517978; hg19: chr5-176761382; API