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GeneBe

20-62309342-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_005560.6(LAMA5):c.11082C>T(p.Ala3694=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,591,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 30)
Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

LAMA5
NM_005560.6 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.461
Variant links:
Genes affected
LAMA5 (HGNC:6485): (laminin subunit alpha 5) This gene encodes one of the vertebrate laminin alpha chains. Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. The protein encoded by this gene is the alpha-5 subunit of of laminin-10 (laminin-511), laminin-11 (laminin-521) and laminin-15 (laminin-523). [provided by RefSeq, Jun 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 20-62309342-G-A is Benign according to our data. Variant chr20-62309342-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2711901.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.461 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LAMA5NM_005560.6 linkuse as main transcriptc.11082C>T p.Ala3694= synonymous_variant 80/80 ENST00000252999.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LAMA5ENST00000252999.7 linkuse as main transcriptc.11082C>T p.Ala3694= synonymous_variant 80/801 NM_005560.6 P1O15230-1
LAMA5ENST00000370691.6 linkuse as main transcriptn.2877C>T non_coding_transcript_exon_variant 17/171
LAMA5ENST00000495695.1 linkuse as main transcriptn.583C>T non_coding_transcript_exon_variant 4/42

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000112
AC:
17
AN:
151970
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000142
AC:
31
AN:
218594
Hom.:
0
AF XY:
0.000173
AC XY:
21
AN XY:
121406
show subpopulations
Gnomad AFR exome
AF:
0.000313
Gnomad AMR exome
AF:
0.0000901
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000208
Gnomad FIN exome
AF:
0.000188
Gnomad NFE exome
AF:
0.000149
Gnomad OTH exome
AF:
0.000184
GnomAD4 exome
AF:
0.000139
AC:
200
AN:
1439252
Hom.:
0
Cov.:
32
AF XY:
0.000149
AC XY:
107
AN XY:
715760
show subpopulations
Gnomad4 AFR exome
AF:
0.000270
Gnomad4 AMR exome
AF:
0.000182
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000152
Gnomad4 SAS exome
AF:
0.000224
Gnomad4 FIN exome
AF:
0.000233
Gnomad4 NFE exome
AF:
0.000109
Gnomad4 OTH exome
AF:
0.000369
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000112
AC:
17
AN:
152088
Hom.:
0
Cov.:
30
AF XY:
0.000148
AC XY:
11
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000117
Hom.:
0
Bravo
AF:
0.000200

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeAug 01, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
Cadd
Benign
5.7
Dann
Benign
0.71
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs553660143; hg19: chr20-60884398; COSMIC: COSV53358408; COSMIC: COSV53358408; API