Genetic Variant NM_005560.6:c.558G>T (chr20-62353144-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_005560.6(LAMA5):c.558G>T(p.Gln186His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q186K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LAMA5
NM_005560.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.37

Publications

1 publications found

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]

LAMA5 links:

LAMA5-AS1 (HGNC:40334): (LAMA5 antisense RNA 1)

LAMA5-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.899

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005560.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LAMA5	NM_005560.6	MANE Select	c.558G>T	p.Gln186His	missense	Exon 3 of 80	NP_005551.3
LAMA5-AS1	NR_109922.1		n.135C>A		non_coding_transcript_exon	Exon 1 of 3
LAMA5-AS1	NR_109923.1		n.135C>A		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LAMA5	ENST00000252999.7	TSL:1 MANE Select	c.558G>T	p.Gln186His	missense	Exon 3 of 80	ENSP00000252999.3	O15230-1
LAMA5	ENST00000370677.4	TSL:2	n.583G>T		non_coding_transcript_exon	Exon 3 of 12
LAMA5-AS1	ENST00000456721.5	TSL:2	n.175C>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1422252

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

703966

African (AFR)

AF:

0.00

AC:

AN:

32624

American (AMR)

AF:

0.00

AC:

AN:

39484

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25328

East Asian (EAS)

AF:

0.00

AC:

AN:

37680

South Asian (SAS)

AF:

0.00

AC:

AN:

81056

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49270

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092228

Other (OTH)

AF:

0.00

AC:

AN:

58860

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.30

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Pathogenic

0.78

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.22

MetaRNN

Pathogenic

0.90

MetaSVM

Uncertain

0.64

MutationAssessor

Pathogenic

3.8

PhyloP100

3.4

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.7

REVEL

Pathogenic

0.83

Sift

Benign

0.057

Sift4G

Uncertain

0.022

Polyphen

1.0

Vest4

0.59

MutPred

0.79

Gain of phosphorylation at Y182 (P = 0.2246)

MVP

0.94

ClinPred

0.99

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.41

gMVP

0.93

Mutation Taster

=47/53

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over