NM_198129.4:c.374G>T

Variant summary

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

The NM_198129.4(LAMA3):​c.374G>T​(p.Arg125Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,613,416 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

LAMA3
NM_198129.4 missense

Scores

1
7
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.82
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]

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
LAMA3NM_198129.4 linkc.374G>T p.Arg125Leu missense_variant Exon 2 of 75 ENST00000313654.14 NP_937762.2 Q16787-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LAMA3ENST00000313654.14 linkc.374G>T p.Arg125Leu missense_variant Exon 2 of 75 1 NM_198129.4 ENSP00000324532.8 Q16787-2
LAMA3ENST00000399516.7 linkc.374G>T p.Arg125Leu missense_variant Exon 2 of 74 1 ENSP00000382432.2 Q16787-3A0A0A0MSA0
LAMA3ENST00000585600.5 linkn.374G>T non_coding_transcript_exon_variant Exon 2 of 13 1 ENSP00000468316.1 A0A075B783

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151656
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461760
Hom.:
0
Cov.:
34
AF XY:
0.00000825
AC XY:
6
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000227
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151656
Hom.:
0
Cov.:
30
AF XY:
0.0000135
AC XY:
1
AN XY:
74022
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Benign
-0.030
T
BayesDel_noAF
Benign
-0.28
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.070
.;T
Eigen
Uncertain
0.20
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.84
.;T
M_CAP
Benign
0.056
D
MetaRNN
Uncertain
0.65
D;D
MetaSVM
Benign
-0.47
T
PrimateAI
Uncertain
0.52
T
PROVEAN
Pathogenic
-5.3
D;D
REVEL
Uncertain
0.42
Sift
Uncertain
0.0080
D;D
Vest4
0.47
MutPred
0.73
Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP
0.75
MPC
0.25
ClinPred
0.97
D
GERP RS
3.9
gMVP
0.73

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

LitVar

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

Other links and lift over

dbSNP: rs374056674; hg19: chr18-21293963; API