rs3810548

chr20-62330822-A-Cchr20-62330822-A-Gchr20-62330822-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005560.6(LAMA5):c.3773T>G(p.Met1258Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,395,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign 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. M1258T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: LAMA5 NM_005560.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.296

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA5	NM_005560.6	c.3773T>G	p.Met1258Arg	missense_variant	30/80	ENST00000252999.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA5	ENST00000252999.7	c.3773T>G	p.Met1258Arg	missense_variant	30/80	1	NM_005560.6	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1395390 Hom.: 0 Cov.: 63 AF XY: 0.00 AC XY: 0 AN XY: 688114

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	11
Dann	Benign	0.39
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	P
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.028
Sift	Benign	0.35	T
Sift4G	Benign	0.65	T
Polyphen		0.0	B
Vest4		0.21
MutPred		0.21		Loss of glycosylation at T1255 (P = 0.1176);
MVP		0.11
ClinPred		0.030	T
GERP RS		1.8
Varity_R		0.066
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: 3

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

Publications

LitVar

Other links and lift over

dbSNP: rs3810548; hg19: chr20-60905878;