18-6942239-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005559.4(LAMA1):​c.9068C>A​(p.Ala3023Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

LAMA1
NM_005559.4 missense, splice_region

Scores

2
17
Splicing: ADA: 0.00005241
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.40
Variant links:
Genes affected
LAMA1 (HGNC:6481): (laminin subunit alpha 1) This gene encodes one of the alpha 1 subunits of laminin. The laminins are a family of extracellular matrix glycoproteins that have a heterotrimeric structure consisting of an alpha, beta and gamma chain. These proteins make up a major component of the basement membrane and have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Mutations in this gene may be associated with Poretti-Boltshauser syndrome. [provided by RefSeq, Sep 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3018179).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LAMA1NM_005559.4 linkuse as main transcriptc.9068C>A p.Ala3023Asp missense_variant, splice_region_variant 63/63 ENST00000389658.4 NP_005550.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LAMA1ENST00000389658.4 linkuse as main transcriptc.9068C>A p.Ala3023Asp missense_variant, splice_region_variant 63/631 NM_005559.4 ENSP00000374309 P1
LAMA1ENST00000488064.5 linkuse as main transcriptn.2475C>A splice_region_variant, non_coding_transcript_exon_variant 14/142
LAMA1ENST00000492048.5 linkuse as main transcriptn.1956C>A splice_region_variant, non_coding_transcript_exon_variant 7/72
LAMA1ENST00000579014.5 linkuse as main transcriptn.10083C>A splice_region_variant, non_coding_transcript_exon_variant 62/622

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152154
Hom.:
0
Cov.:
33
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:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000121
AC:
3
AN:
248608
Hom.:
0
AF XY:
0.00000743
AC XY:
1
AN XY:
134634
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461664
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727132
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152272
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

Ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingRevvity Omics, RevvityFeb 06, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.090
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
18
DANN
Benign
0.81
DEOGEN2
Benign
0.014
T
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.33
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
0.94
L
MutationTaster
Benign
0.93
D
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-1.5
N
REVEL
Uncertain
0.37
Sift
Benign
1.0
T
Sift4G
Benign
0.20
T
Polyphen
0.69
P
Vest4
0.48
MutPred
0.41
Gain of ubiquitination at K3026 (P = 0.0359);
MVP
0.72
MPC
0.62
ClinPred
0.16
T
GERP RS
4.8
Varity_R
0.082
gMVP
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000052
dbscSNV1_RF
Benign
0.0080
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: rs527377399; hg19: chr18-6942238; API