chr12-91108169-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002345.4(LUM):​c.811A>G​(p.Thr271Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

LUM
NM_002345.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.19
Variant links:
Genes affected
LUM (HGNC:6724): (lumican) This gene encodes a member of the small leucine-rich proteoglycan (SLRP) family that includes decorin, biglycan, fibromodulin, keratocan, epiphycan, and osteoglycin. In these bifunctional molecules, the protein moiety binds collagen fibrils and the highly charged hydrophilic glycosaminoglycans regulate interfibrillar spacings. Lumican is the major keratan sulfate proteoglycan of the cornea but is also distributed in interstitial collagenous matrices throughout the body. Lumican may regulate collagen fibril organization and circumferential growth, corneal transparency, and epithelial cell migration and tissue repair. [provided by RefSeq, Jul 2008]

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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=0.081307024).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LUMNM_002345.4 linkuse as main transcriptc.811A>G p.Thr271Ala missense_variant 2/3 ENST00000266718.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LUMENST00000266718.5 linkuse as main transcriptc.811A>G p.Thr271Ala missense_variant 2/31 NM_002345.4 P1
LUMENST00000546642.1 linkuse as main transcriptn.561A>G non_coding_transcript_exon_variant 2/33
LUMENST00000548071.1 linkuse as main transcriptn.204A>G non_coding_transcript_exon_variant 2/33

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
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 submitterclinical testingAmbry GeneticsFeb 17, 2022The c.811A>G (p.T271A) alteration is located in exon 2 (coding exon 1) of the LUM gene. This alteration results from a A to G substitution at nucleotide position 811, causing the threonine (T) at amino acid position 271 to be replaced by an alanine (A). 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
0.059
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
15
DANN
Benign
0.78
DEOGEN2
Benign
0.30
T
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.24
FATHMM_MKL
Benign
0.72
D
LIST_S2
Benign
0.69
T
M_CAP
Benign
0.0045
T
MetaRNN
Benign
0.081
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
L
MutationTaster
Benign
0.50
D
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.46
N
REVEL
Benign
0.057
Sift
Benign
0.77
T
Sift4G
Benign
0.84
T
Polyphen
0.0
B
Vest4
0.066
MutPred
0.29
Loss of methylation at K267 (P = 0.1104);
MVP
0.33
MPC
0.37
ClinPred
0.13
T
GERP RS
4.4
Varity_R
0.061
gMVP
0.28

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-91501946; API