rs2076222

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_000228.3(LAMB3):​c.2777C>G​(p.Ala926Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A926D) has been classified as Benign.

Frequency

Genomes: not found (cov: 34)

Consequence

LAMB3
NM_000228.3 missense

Scores

6
13

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.32
Variant links:
Genes affected
LAMB3 (HGNC:6490): (laminin subunit beta 3) The product encoded by this gene is a laminin that belongs to a family of basement membrane proteins. This protein is a beta subunit laminin, which together with an alpha and a gamma subunit, forms laminin-5. Mutations in this gene cause epidermolysis bullosa junctional Herlitz type, and generalized atrophic benign epidermolysis bullosa, diseases that are characterized by blistering of the skin. Multiple alternatively spliced transcript variants that encode the same protein have been found for this gene. [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;
BP6
Variant 1-209618584-G-C is Benign according to our data. Variant chr1-209618584-G-C is described in ClinVar as [Benign]. Clinvar id is 1291217.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LAMB3NM_000228.3 linkuse as main transcriptc.2777C>G p.Ala926Gly missense_variant 19/23 ENST00000356082.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LAMB3ENST00000356082.9 linkuse as main transcriptc.2777C>G p.Ala926Gly missense_variant 19/231 NM_000228.3 P1
LAMB3ENST00000367030.7 linkuse as main transcriptc.2777C>G p.Ala926Gly missense_variant 19/231 P1
LAMB3ENST00000391911.5 linkuse as main transcriptc.2777C>G p.Ala926Gly missense_variant 18/221 P1
LAMB3ENST00000455193.1 linkuse as main transcriptc.-17C>G 5_prime_UTR_variant 1/42

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
34

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
T;T;T
Eigen
Benign
0.17
Eigen_PC
Benign
0.032
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.79
.;T;.
M_CAP
Benign
0.062
D
MetaRNN
Uncertain
0.71
D;D;D
MetaSVM
Benign
-0.65
T
MutationAssessor
Uncertain
2.6
M;M;M
MutationTaster
Benign
0.25
P;P;P
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-1.4
N;N;N
REVEL
Benign
0.21
Sift
Uncertain
0.014
D;D;D
Sift4G
Uncertain
0.023
D;D;D
Polyphen
0.99
D;D;D
Vest4
0.39
MutPred
0.57
Gain of catalytic residue at A926 (P = 0.0169);Gain of catalytic residue at A926 (P = 0.0169);Gain of catalytic residue at A926 (P = 0.0169);
MVP
0.68
MPC
0.14
ClinPred
0.71
D
GERP RS
4.1
Varity_R
0.13
gMVP
0.10

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.18
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: chr1-209791929; API