rs944895

chr20-62312525-G-Achr20-62312525-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005560.6(LAMA5):c.9235C>T(p.Arg3079Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,598,442 control chromosomes in the GnomAD database, including 337,535 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.64 (31844 hom., cov: 35)
  • Exomes 𝑓: 0.65 (305691 hom.)
• Consequence: LAMA5 NM_005560.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.130

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.0983107E-6).
• BP6: Variant 20-62312525-G-A is Benign according to our data. Variant chr20-62312525-G-A is described in ClinVar as [Benign]. Clinvar id is 1297290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA5	NM_005560.6	c.9235C>T	p.Arg3079Trp	missense_variant	68/80	ENST00000252999.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA5	ENST00000252999.7	c.9235C>T	p.Arg3079Trp	missense_variant	68/80	1	NM_005560.6	P1
LAMA5	ENST00000370691.6	n.1184C>T		non_coding_transcript_exon_variant	6/17	1
LAMA5	ENST00000491036.2	n.338C>T		non_coding_transcript_exon_variant	2/4	2

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97928 AN: 152022 Hom.: 31821 Cov.: 35

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.655

GnomAD3 exomes AF: 0.678 AC: 159299 AN: 235114 Hom.: 54299 AF XY: 0.679 AC XY: 87446 AN XY: 128826

Gnomad AFR exome AF: 0.567

Gnomad AMR exome AF: 0.730

Gnomad ASJ exome AF: 0.714

Gnomad EAS exome AF: 0.732

Gnomad SAS exome AF: 0.731

Gnomad FIN exome AF: 0.698

Gnomad NFE exome AF: 0.648

Gnomad OTH exome AF: 0.677

GnomAD4 exome AF: 0.648 AC: 937854 AN: 1446302 Hom.: 305691 Cov.: 81 AF XY: 0.651 AC XY: 468655 AN XY: 719952

Gnomad4 AFR exome AF: 0.572

Gnomad4 AMR exome AF: 0.723

Gnomad4 ASJ exome AF: 0.719

Gnomad4 EAS exome AF: 0.729

Gnomad4 SAS exome AF: 0.728

Gnomad4 FIN exome AF: 0.697

Gnomad4 NFE exome AF: 0.634

Gnomad4 OTH exome AF: 0.666

GnomAD4 genome AF: 0.644 AC: 97985 AN: 152140 Hom.: 31844 Cov.: 35 AF XY: 0.651 AC XY: 48438 AN XY: 74384

Gnomad4 AFR AF: 0.568

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.756

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.658

Alfa AF: 0.655 Hom.: 58729

Bravo AF: 0.639

TwinsUK AF: 0.643 AC: 2386

ALSPAC AF: 0.633 AC: 2440

ESP6500AA AF: 0.570 AC: 2500

ESP6500EA AF: 0.652 AC: 5600

ExAC AF: 0.670 AC: 80085

Asia WGS AF: 0.751 AC: 2614 AN: 3478

EpiCase AF: 0.646

EpiControl AF: 0.645

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 22, 2019	This variant is associated with the following publications: (PMID: 23264881, 18694491) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	18
Dann	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.0000061	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.98	D
Vest4		0.085
ClinPred		0.021	T
GERP RS		3.4
Varity_R		0.11
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs944895; hg19: chr20-60887581; COSMIC: COSV53354200; COSMIC: COSV53354200;