GeneBe

18-23901376-A-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198129.4(LAMA3):​c.6201+53A>T variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

LAMA3
NM_198129.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.623

Publications

11 publications found
Variant links:
Genes affected
LAMA3 (HGNC:6483): (laminin subunit alpha 3) The protein encoded by this gene belongs to the laminin family of secreted molecules. Laminins are heterotrimeric molecules that consist of alpha, beta, and gamma subunits that assemble through a coiled-coil domain. Laminins are essential for formation and function of the basement membrane and have additional functions in regulating cell migration and mechanical signal transduction. This gene encodes an alpha subunit and is responsive to several epithelial-mesenchymal regulators including keratinocyte growth factor, epidermal growth factor and insulin-like growth factor. Mutations in this gene have been identified as the cause of Herlitz type junctional epidermolysis bullosa and laryngoonychocutaneous syndrome. Alternative splicing and alternative promoter usage result in multiple transcript variants. [provided by RefSeq, Dec 2014]
LAMA3 Gene-Disease associations (from GenCC):
  • junctional epidermolysis bullosa
    Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
  • laryngo-onycho-cutaneous syndrome
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
  • junctional epidermolysis bullosa Herlitz type
    Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
  • junctional epidermolysis bullosa, non-Herlitz type
    Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Genomics England PanelApp
  • generalized junctional epidermolysis bullosa non-Herlitz type
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LAMA3NM_198129.4 linkc.6201+53A>T intron_variant Intron 48 of 74 ENST00000313654.14 NP_937762.2 Q16787-2
LAMA3NM_000227.6 linkc.1374+53A>T intron_variant Intron 11 of 37 ENST00000269217.11 NP_000218.3 Q16787-1A0A0A6YYF2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LAMA3ENST00000313654.14 linkc.6201+53A>T intron_variant Intron 48 of 74 1 NM_198129.4 ENSP00000324532.8 Q16787-2
LAMA3ENST00000269217.11 linkc.1374+53A>T intron_variant Intron 11 of 37 1 NM_000227.6 ENSP00000269217.5 Q16787-1A0A0A6YYF2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1302276
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
655850
African (AFR)
AF:
0.00
AC:
0
AN:
30472
American (AMR)
AF:
0.00
AC:
0
AN:
44124
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25190
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38890
South Asian (SAS)
AF:
0.00
AC:
0
AN:
82290
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52898
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4062
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
969394
Other (OTH)
AF:
0.00
AC:
0
AN:
54956
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
1.1
DANN
Benign
0.83
PhyloP100
-0.62

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

Other links and lift over

dbSNP: rs1154227; hg19: chr18-21481340; API