20-62330822-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005560.6(LAMA5):c.3773T>C(p.Met1258Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 1,547,168 control chromosomes in the GnomAD database, including 625,037 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

Frequency

Genomes: 𝑓 0.80 ( 50275 hom., cov: 31)

Exomes 𝑓: 0.90 ( 574762 hom. )

Consequence

LAMA5
NM_005560.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.296

Publications

28 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 Gene-Disease associations (from GenCC):

nephrotic syndrome, IIa 26
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
LAMA5-related multisystemic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LAMA5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.261096E-7).

BP6

Variant 20-62330822-A-G is Benign according to our data. Variant chr20-62330822-A-G is described in ClinVar as Benign. ClinVar VariationId is 1233173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA5	NM_005560.6 link	c.3773T>C	p.Met1258Thr	missense_variant	Exon 30 of 80	ENST00000252999.7	NP_005551.3	O15230-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA5	ENST00000252999.7 link	c.3773T>C	p.Met1258Thr	missense_variant	Exon 30 of 80	1	NM_005560.6	ENSP00000252999.3		O15230-1

Frequencies

GnomAD3 genomes

AF:

0.796

AC:

120941

AN:

151864

Hom.:

50268

Cov.:

show subpopulations

Gnomad AFR

AF:

0.534

Gnomad AMI

AF:

0.948

Gnomad AMR

AF:

0.803

Gnomad ASJ

AF:

0.903

Gnomad EAS

AF:

0.942

Gnomad SAS

AF:

0.800

Gnomad FIN

AF:

0.852

Gnomad MID

AF:

0.831

Gnomad NFE

AF:

0.925

Gnomad OTH

AF:

0.840

GnomAD2 exomes

AF:

0.859

AC:

135333

AN:

157512

AF XY:

0.864

show subpopulations

Gnomad AFR exome

AF:

0.518

Gnomad AMR exome

AF:

0.818

Gnomad ASJ exome

AF:

0.896

Gnomad EAS exome

AF:

0.952

Gnomad FIN exome

AF:

0.854

Gnomad NFE exome

AF:

0.925

Gnomad OTH exome

AF:

0.866

GnomAD4 exome

AF:

0.905

AC:

1262294

AN:

1395186

Hom.:

574762

Cov.:

AF XY:

0.903

AC XY:

621480

AN XY:

688008

show subpopulations

African (AFR)

AF:

0.513

AC:

16322

AN:

31824

American (AMR)

AF:

0.815

AC:

29169

AN:

35804

Ashkenazi Jewish (ASJ)

AF:

0.899

AC:

22126

AN:

24604

East Asian (EAS)

AF:

0.953

AC:

34372

AN:

36072

South Asian (SAS)

AF:

0.802

AC:

63206

AN:

78802

European-Finnish (FIN)

AF:

0.852

AC:

39278

AN:

46116

Middle Eastern (MID)

AF:

0.850

AC:

4789

AN:

5636

European-Non Finnish (NFE)

AF:

0.929

AC:

1001924

AN:

1078504

Other (OTH)

AF:

0.884

AC:

51108

AN:

57824

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

6469

12938

19408

25877

32346

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21128

42256

63384

84512

105640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.796

AC:

121000

AN:

151982

Hom.:

50275

Cov.:

AF XY:

0.793

AC XY:

58902

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.534

AC:

22134

AN:

41418

American (AMR)

AF:

0.803

AC:

12267

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.903

AC:

3133

AN:

3468

East Asian (EAS)

AF:

0.942

AC:

4813

AN:

5110

South Asian (SAS)

AF:

0.800

AC:

3861

AN:

4828

European-Finnish (FIN)

AF:

0.852

AC:

9021

AN:

10588

Middle Eastern (MID)

AF:

0.825

AC:

241

AN:

292

European-Non Finnish (NFE)

AF:

0.925

AC:

62890

AN:

67972

Other (OTH)

AF:

0.841

AC:

1777

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1027

2053

3080

4106

5133

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

858

1716

2574

3432

4290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.876

Hom.:

28623

Bravo

AF:

0.783

TwinsUK

AF:

0.936

AC:

3470

ALSPAC

AF:

0.927

AC:

3571

ESP6500AA

AF:

0.565

AC:

2406

ESP6500EA

AF:

0.929

AC:

7826

ExAC

AF:

0.825

AC:

86413

Asia WGS

AF:

0.837

AC:

2911

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 10, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 19435634) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.3

(source)

DANN

Benign

0.29

DEOGEN2

Benign

0.013

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.087

MetaRNN

Benign

8.3e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PhyloP100

0.30

PrimateAI

Uncertain

0.50

PROVEAN

Benign

1.1

REVEL

Benign

0.037

Sift

Benign

0.45

Sift4G

Benign

0.77

Polyphen

0.0

Vest4

0.029

ClinPred

0.0027

GERP RS

1.8

Varity_R

0.021

gMVP

0.26

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over